Retinal photoreceptor cells, rods and cones, convert photons of light into chemical and electrica... more Retinal photoreceptor cells, rods and cones, convert photons of light into chemical and electrical signals as the first step of the visual transduction cascade. Although the chemical processes in the phototransduction system are very similar to each other in these photoreceptors, the light sensitivity and time resolution of the photoresponse in rods are functionally different than those in the photoresponses of cones. To systematically investigate how photoresponses are divergently regulated in rods and cones, we have developed a detailed mathematical model on the basis of the Hamer model. The current model successfully reconstructed light intensity-, ATP- and GTP-dependent changes in concentrations of phosphorylated visual pigments (VPs), activated transducins (Tr*s) and phosphodiesterases (PDEs), as well as cyclic nucleotide-gated currents (ICNG) in rods and cones. In comparison to rods, the lower light sensitivity of cones was attributed not only to the lower affinity of activate...
American journal of physiology. Cell physiology, Jan 25, 2015
GLP-1 is an intestinally derived blood glucose-lowering hormone that potentiates glucose-stimulat... more GLP-1 is an intestinally derived blood glucose-lowering hormone that potentiates glucose-stimulated insulin secretion from pancreatic β-cells. This secretagogue action of GLP-1 is explained, at least in part, by its ability to stimulate cAMP production so that cAMP may facilitate the release of Ca(2+) from IP3 receptor (IP3R)-regulated Ca(2+) stores. However, a quantitative model has yet to be provided that explains the molecular mechanisms and dynamic processes linking GLP-1-stimulated cAMP production to Ca(2+) mobilization. Here, we performed simulation studies to investigate how GLP-1 alters the abilities of Ca(2+) and IP3 to act as co-agonists at IP3R Ca(2+) release channels. A new dynamic model was constructed based on the Kaftan model, which demonstrates dual steady state allosteric regulation of the IP3R by Ca(2+) and IP3. Data obtained from β-cells were then analyzed to understand how GLP-1 facilitates IP3R-mediated Ca(2+) mobilization when UV flash photolysis is used to unc...
Synaptic specializations exist between enteric motor nerves and interstitial cells of Cajal in the murine stomach
The Journal of Comparative Neurology, 2005
Autonomic neurotransmission is thought to occur via a loose association between nerve varicositie... more Autonomic neurotransmission is thought to occur via a loose association between nerve varicosities and smooth muscle cells. In the gastrointestinal tract ultrastructural studies have demonstrated close apposition between enteric nerves and intramuscular interstitial cells of Cajal (ICC-IM) in the stomach and colon and ICC in the deep muscular plexus (ICC-DMP) of the small intestine. In the absence of ICC-IM, postjunctional neural responses are compromised. Although membrane specializations between nerves and ICC-IM have been reported, the molecular identity of these specializations has not been studied. Here we have characterized the expression and distribution of synapse-associated proteins between nerve terminals and ICC-IM in the murine stomach. Transcripts for the presynaptic proteins synaptotagmin, syntaxin, and SNAP-25 were detected. Synaptotagmin and SNAP-25-immunopositive nerve varicosities were concentrated in varicose regions of motor nerves and were closely apposed to ICC-IM but not smooth muscle. W/W(V) mice were used to examine the expression and distribution of synaptic proteins in the absence of ICC-IM. Transcripts encoding synaptotagmin, syntaxin, and SNAP-25 were detected in W/W(V) tissues. In the absence of ICC-IM, synaptotagmin and SNAP-25 were localized to nerve varicosities. Reverse transcriptase polymer chain reaction (RT-PCR) and immunohistochemistry demonstrated the expression of postsynaptic density proteins PSD-93 and PSD-95 in the stomach and expression levels of PSD-93 and PSD-95 were reduced in W/W(V) mutants. These data support the existence of synaptic specializations between enteric nerves and ICC-IM in gastric tissues. In the absence of ICC-IM, components of the synaptic vesicle docking and fusion machinery is trafficked and concentrated in enteric nerve terminals.
American Journal of Physiology-Heart and Circulatory Physiology, 2011
Ca+sparklets are subcellular Ca2+signals produced by the opening of sarcolemmal L-type Ca2+channe... more Ca+sparklets are subcellular Ca2+signals produced by the opening of sarcolemmal L-type Ca2+channels. Ca2+sparklet activity varies within the sarcolemma of arterial myocytes. In this study, we examined the relationship between Ca2+sparklet activity and sarcoplasmic reticulum (SR) Ca2+accumulation and release in cerebral arterial myocytes. Our data indicate that the SR is a vast organelle with multiple regions near the sarcolemma of these cells. Ca2+sparklet sites were located at or <0.2 μm from SR-sarcolemmal junctions. We found that while Ca2+sparklets increase the rate of SR Ca2+refilling in arterial myocytes, their activity did not induce regional variations in SR Ca2+content or Ca2+spark activity. In arterial myocytes, L-type Ca2+channel activity was independent of SR Ca2+load. This ruled out a potential feedback mechanism whereby SR Ca2+load regulates the activity of these channels. Together, our data suggest a model in which Ca2+sparklets contribute Ca2+influx into a cytosol...
American Journal of Physiology-Gastrointestinal and Liver Physiology, 2005
In the tunica muscularis of the gastrointestinal (GI) tract, gap junctions form low-resistance pa... more In the tunica muscularis of the gastrointestinal (GI) tract, gap junctions form low-resistance pathways between pacemaker cells known as interstitial cells of Cajal (ICCs) and between ICC and smooth muscle cells. Coupling via these junctions facilitates electrical slow-wave propagation and responses of smooth muscle to enteric motor nerves. Glycyrrhetinic acid (GA) has been shown to uncouple gap junctions, but previous studies have shown apparent nonspecific effects of GA in a variety of tissues. We tested the effects of GA using isometric force measurements, intracellular microelectrode recordings, the patch-clamp technique, and the spread of Lucifer yellow within cultured ICC networks. In murine small intestinal muscles, β-GA (10 μM) decreased phasic contractions and depolarized resting membrane potential. Preincubation of GA inhibited the spread of Lucifer yellow, increased input resistance, and decreased cell capacitance in ICC networks, suggesting that GA uncoupled ICCs. In pat...
American Journal of Physiology-Cell Physiology, 2011
Glucagon-like peptide-1 (GLP-1) elevates intracellular concentration of cAMP ([cAMP]) and facilit... more Glucagon-like peptide-1 (GLP-1) elevates intracellular concentration of cAMP ([cAMP]) and facilitates glucose-dependent insulin secretion in pancreatic β-cells. There has been much evidence to suggest that multiple key players such as the GLP-1 receptor, Gsprotein, adenylate cyclase (AC), phosphodiesterase (PDE), and intracellular Ca2+concentration ([Ca2+]) are involved in the regulation of [cAMP]. However, because of complex interactions among these signaling factors, the kinetics of the reaction cascade as well as the activities of ACs and PDEs have not been determined in pancreatic β-cells. We have constructed a minimal mathematical model of GLP-1 receptor signal transduction based on experimental findings obtained mostly in β-cells and insulinoma cell lines. By fitting this theoretical reaction scheme to key experimental records of the GLP-1 response, the parameters determining individual reaction steps were estimated. The model reconstructed satisfactorily the dynamic changes i...
Two distinct populations of interstitial cells of Cajal (ICC) exist within the tunica muscularis ... more Two distinct populations of interstitial cells of Cajal (ICC) exist within the tunica muscularis of the gastric antrum, and these cells serve different physiological functions. One population of ICC generates and actively propagates electrical slow waves, and the other population of ICC is innervated by excitatory and inhibitory motor neurons and mediates enteric motor neurotransmission. In spite of the key role of ICC in gastric excitability, little is known about the ionic conductances that underlie the functional diversity of these cells. In the present study we isolated ICC from the murine gastric antrum and investigated the Ca 2+-dependent ionic conductances expressed by these cells using the patch clamp technique. Conductances in ICC were compared with those expressed in smooth muscle cells. The cells studied were identified by RT-PCR using cell-specific primers that included Myh11 (smooth muscle cells), Kit (ICC) and Uchl1 (enteric neurons) following electrophysiolgical recordings. Distinct ionic conductances were observed in Kit-positive cells. One group of ICC expressed a basal non-selective cation conductance (NSCC) that was inhibited by an increase in [Ca 2+ ] i in a calmodulin (CaM)-dependent manner. A second population of ICC generated spontaneous transient inward currents (STICs) and expressed a basal noisy NSCC that was facilitated by an increase in [Ca 2+ ] i in a CaM-dependent manner. The [Ca 2+ ] i-facilitated NSCC in ICC was blocked by the Cl − channel antagonists 4,4-diisothiocyanatostilbene-2,2-disulphonic acid (DIDS), anthracene-9-carboxylate (9-AC) and niflumic acid. These data suggest that distinct NSCC are expressed in subpopulations of ICC and these conductances may underlie the functional differences of these cells within the gastric antrum.
Visual impairment has serious impact on our quality of life. Although stem cell-based therapies c... more Visual impairment has serious impact on our quality of life. Although stem cell-based therapies contribute to improve retinal diseases, it is essentially critical to have quantitative data of the physiological characteristics of retinal cellular functions and related neural networks for reliable treatment. In the phototransduction system of retinal photoreceptor cells, visual pigments are activated by the incident light and stimulate transducin, which in turn send electrical signals to downstream neural networks. A single visual pigment may activate hundreds of transducin, amplifying the incoming signal. Efficacy of the signal amplification system has been reported to be light intensity-dependent. Experimentally, a positive correlation between light intensity and activated transducin has been observed at a lower stimulation intensity range, whereas activated transducin starts to decrease at very high intensity light stimulation. Since none of the proposed phototransduction models were able to reproduce the complex characteristics of the signal transduction system of retinal photoreceptor cells, we propose a model that may reproduce the light intensity-dependent amplification of incoming signals in both rods and cones. The present model successfully reproduced the experimental data.
Upon elevation of plasma glucose concentration, pancreatic b-cells generate bursts of action pote... more Upon elevation of plasma glucose concentration, pancreatic b-cells generate bursts of action potentials to induce cyclic changes in [Ca 2＋ ] i regulating insulin release. Glucose-dependent insulin secretion is synergistically enhanced by glucagon-like peptide-1 (GLP-1), which increases [cAMP] i and activates protein kinase A (PKA) and exchange protein activated by cAMP (Epac). The insulinotropic eŠect of GLP-1 is mediated, at least in part, by modulating multiple ion channels/transporters at the plasma membrane and ER through PKA-and EPAC-dependent mechanisms, which increase membrane excitability and intracellular Ca 2＋ release. However, because of complex interactions between multiple cellular factors involved in the GLP-1 eŠects, quantitative aspects of the molecular/ionic mechanisms have not yet been determined. We thus performed simulation studies and mathematical analysis to investigate how GLP-1 signals control [cAMP] i and subsequently modify the bursting activities and Ca 2＋ dynamics. First, a GLP-1 receptor signal transduction model was developed and introduced to our b-cells model. Secondly, modulatory eŠects of PKA/Epac on ion channels/transporters were incorporated based on experimental studies. Increases in the frequency and duration of the bursting activity observed during GLP-1 stimulation were well reconstructed by our model, and lead potential analysis quantitatively determined the functional role of each ion channel/transporter in modifying the burst pattern. Finally, an IP 3 R model was developed to reproduce GLP-1-induced Ca 2＋ transients/oscillations. Instantaneous equilibrium analysis and bifurcation analysis also elucidated the quantitative mechanisms involved in generating IP 3 R-mediated Ca 2＋ mobilization. The results of this theoretical analysis of the eŠects of GLP-1 on membrane excitability/Ca 2＋ dynamics are discussed in this review.
Ca+ sparklets are subcellular Ca2+ signals produced by the opening of L-type Ca2+ channels (LTCCs... more Ca+ sparklets are subcellular Ca2+ signals produced by the opening of L-type Ca2+ channels (LTCCs). In cerebral arterial myocytes, Ca2+ sparklet activity varies regionally, resulting in low and high activity, “persistent” Ca2+ sparklet sites. Although increased Ca2+ influx via LTCCs in arterial myocytes has been implicated in the chain of events contributing to vascular dysfunction during acute hyperglycemia and diabetes, the mechanisms underlying these pathological changes remain unclear. Here, we tested the hypothesis that increased Ca2+ sparklet activity contributes to higher Ca2+ influx in cerebral artery smooth muscle during acute hyperglycemia and in an animal model of non-insulin-dependent, type 2 diabetes: the dB/dB mouse. Consistent with this hypothesis, acute elevation of extracellular glucose from 10 to 20 mM increased the density of low activity and persistent Ca2+ sparklet sites as well as the amplitude of LTCC currents in wild-type cerebral arterial myocytes. Furthermo...
Retinal photoreceptor cells, rods and cones, convert photons of light into chemical and electrica... more Retinal photoreceptor cells, rods and cones, convert photons of light into chemical and electrical signals as the first step of the visual transduction cascade. Although the chemical processes in the phototransduction system are very similar to each other in these photoreceptors, the light sensitivity and time resolution of the photoresponse in rods are functionally different than those in the photoresponses of cones. To systematically investigate how photoresponses are divergently regulated in rods and cones, we have developed a detailed mathematical model on the basis of the Hamer model. The current model successfully reconstructed light intensity-, ATP- and GTP-dependent changes in concentrations of phosphorylated visual pigments (VPs), activated transducins (Tr*s) and phosphodiesterases (PDEs), as well as cyclic nucleotide-gated currents (ICNG) in rods and cones. In comparison to rods, the lower light sensitivity of cones was attributed not only to the lower affinity of activate...
American journal of physiology. Cell physiology, Jan 25, 2015
GLP-1 is an intestinally derived blood glucose-lowering hormone that potentiates glucose-stimulat... more GLP-1 is an intestinally derived blood glucose-lowering hormone that potentiates glucose-stimulated insulin secretion from pancreatic β-cells. This secretagogue action of GLP-1 is explained, at least in part, by its ability to stimulate cAMP production so that cAMP may facilitate the release of Ca(2+) from IP3 receptor (IP3R)-regulated Ca(2+) stores. However, a quantitative model has yet to be provided that explains the molecular mechanisms and dynamic processes linking GLP-1-stimulated cAMP production to Ca(2+) mobilization. Here, we performed simulation studies to investigate how GLP-1 alters the abilities of Ca(2+) and IP3 to act as co-agonists at IP3R Ca(2+) release channels. A new dynamic model was constructed based on the Kaftan model, which demonstrates dual steady state allosteric regulation of the IP3R by Ca(2+) and IP3. Data obtained from β-cells were then analyzed to understand how GLP-1 facilitates IP3R-mediated Ca(2+) mobilization when UV flash photolysis is used to unc...
Synaptic specializations exist between enteric motor nerves and interstitial cells of Cajal in the murine stomach
The Journal of Comparative Neurology, 2005
Autonomic neurotransmission is thought to occur via a loose association between nerve varicositie... more Autonomic neurotransmission is thought to occur via a loose association between nerve varicosities and smooth muscle cells. In the gastrointestinal tract ultrastructural studies have demonstrated close apposition between enteric nerves and intramuscular interstitial cells of Cajal (ICC-IM) in the stomach and colon and ICC in the deep muscular plexus (ICC-DMP) of the small intestine. In the absence of ICC-IM, postjunctional neural responses are compromised. Although membrane specializations between nerves and ICC-IM have been reported, the molecular identity of these specializations has not been studied. Here we have characterized the expression and distribution of synapse-associated proteins between nerve terminals and ICC-IM in the murine stomach. Transcripts for the presynaptic proteins synaptotagmin, syntaxin, and SNAP-25 were detected. Synaptotagmin and SNAP-25-immunopositive nerve varicosities were concentrated in varicose regions of motor nerves and were closely apposed to ICC-IM but not smooth muscle. W/W(V) mice were used to examine the expression and distribution of synaptic proteins in the absence of ICC-IM. Transcripts encoding synaptotagmin, syntaxin, and SNAP-25 were detected in W/W(V) tissues. In the absence of ICC-IM, synaptotagmin and SNAP-25 were localized to nerve varicosities. Reverse transcriptase polymer chain reaction (RT-PCR) and immunohistochemistry demonstrated the expression of postsynaptic density proteins PSD-93 and PSD-95 in the stomach and expression levels of PSD-93 and PSD-95 were reduced in W/W(V) mutants. These data support the existence of synaptic specializations between enteric nerves and ICC-IM in gastric tissues. In the absence of ICC-IM, components of the synaptic vesicle docking and fusion machinery is trafficked and concentrated in enteric nerve terminals.
American Journal of Physiology-Heart and Circulatory Physiology, 2011
Ca+sparklets are subcellular Ca2+signals produced by the opening of sarcolemmal L-type Ca2+channe... more Ca+sparklets are subcellular Ca2+signals produced by the opening of sarcolemmal L-type Ca2+channels. Ca2+sparklet activity varies within the sarcolemma of arterial myocytes. In this study, we examined the relationship between Ca2+sparklet activity and sarcoplasmic reticulum (SR) Ca2+accumulation and release in cerebral arterial myocytes. Our data indicate that the SR is a vast organelle with multiple regions near the sarcolemma of these cells. Ca2+sparklet sites were located at or <0.2 μm from SR-sarcolemmal junctions. We found that while Ca2+sparklets increase the rate of SR Ca2+refilling in arterial myocytes, their activity did not induce regional variations in SR Ca2+content or Ca2+spark activity. In arterial myocytes, L-type Ca2+channel activity was independent of SR Ca2+load. This ruled out a potential feedback mechanism whereby SR Ca2+load regulates the activity of these channels. Together, our data suggest a model in which Ca2+sparklets contribute Ca2+influx into a cytosol...
American Journal of Physiology-Gastrointestinal and Liver Physiology, 2005
In the tunica muscularis of the gastrointestinal (GI) tract, gap junctions form low-resistance pa... more In the tunica muscularis of the gastrointestinal (GI) tract, gap junctions form low-resistance pathways between pacemaker cells known as interstitial cells of Cajal (ICCs) and between ICC and smooth muscle cells. Coupling via these junctions facilitates electrical slow-wave propagation and responses of smooth muscle to enteric motor nerves. Glycyrrhetinic acid (GA) has been shown to uncouple gap junctions, but previous studies have shown apparent nonspecific effects of GA in a variety of tissues. We tested the effects of GA using isometric force measurements, intracellular microelectrode recordings, the patch-clamp technique, and the spread of Lucifer yellow within cultured ICC networks. In murine small intestinal muscles, β-GA (10 μM) decreased phasic contractions and depolarized resting membrane potential. Preincubation of GA inhibited the spread of Lucifer yellow, increased input resistance, and decreased cell capacitance in ICC networks, suggesting that GA uncoupled ICCs. In pat...
American Journal of Physiology-Cell Physiology, 2011
Glucagon-like peptide-1 (GLP-1) elevates intracellular concentration of cAMP ([cAMP]) and facilit... more Glucagon-like peptide-1 (GLP-1) elevates intracellular concentration of cAMP ([cAMP]) and facilitates glucose-dependent insulin secretion in pancreatic β-cells. There has been much evidence to suggest that multiple key players such as the GLP-1 receptor, Gsprotein, adenylate cyclase (AC), phosphodiesterase (PDE), and intracellular Ca2+concentration ([Ca2+]) are involved in the regulation of [cAMP]. However, because of complex interactions among these signaling factors, the kinetics of the reaction cascade as well as the activities of ACs and PDEs have not been determined in pancreatic β-cells. We have constructed a minimal mathematical model of GLP-1 receptor signal transduction based on experimental findings obtained mostly in β-cells and insulinoma cell lines. By fitting this theoretical reaction scheme to key experimental records of the GLP-1 response, the parameters determining individual reaction steps were estimated. The model reconstructed satisfactorily the dynamic changes i...
Two distinct populations of interstitial cells of Cajal (ICC) exist within the tunica muscularis ... more Two distinct populations of interstitial cells of Cajal (ICC) exist within the tunica muscularis of the gastric antrum, and these cells serve different physiological functions. One population of ICC generates and actively propagates electrical slow waves, and the other population of ICC is innervated by excitatory and inhibitory motor neurons and mediates enteric motor neurotransmission. In spite of the key role of ICC in gastric excitability, little is known about the ionic conductances that underlie the functional diversity of these cells. In the present study we isolated ICC from the murine gastric antrum and investigated the Ca 2+-dependent ionic conductances expressed by these cells using the patch clamp technique. Conductances in ICC were compared with those expressed in smooth muscle cells. The cells studied were identified by RT-PCR using cell-specific primers that included Myh11 (smooth muscle cells), Kit (ICC) and Uchl1 (enteric neurons) following electrophysiolgical recordings. Distinct ionic conductances were observed in Kit-positive cells. One group of ICC expressed a basal non-selective cation conductance (NSCC) that was inhibited by an increase in [Ca 2+ ] i in a calmodulin (CaM)-dependent manner. A second population of ICC generated spontaneous transient inward currents (STICs) and expressed a basal noisy NSCC that was facilitated by an increase in [Ca 2+ ] i in a CaM-dependent manner. The [Ca 2+ ] i-facilitated NSCC in ICC was blocked by the Cl − channel antagonists 4,4-diisothiocyanatostilbene-2,2-disulphonic acid (DIDS), anthracene-9-carboxylate (9-AC) and niflumic acid. These data suggest that distinct NSCC are expressed in subpopulations of ICC and these conductances may underlie the functional differences of these cells within the gastric antrum.
Visual impairment has serious impact on our quality of life. Although stem cell-based therapies c... more Visual impairment has serious impact on our quality of life. Although stem cell-based therapies contribute to improve retinal diseases, it is essentially critical to have quantitative data of the physiological characteristics of retinal cellular functions and related neural networks for reliable treatment. In the phototransduction system of retinal photoreceptor cells, visual pigments are activated by the incident light and stimulate transducin, which in turn send electrical signals to downstream neural networks. A single visual pigment may activate hundreds of transducin, amplifying the incoming signal. Efficacy of the signal amplification system has been reported to be light intensity-dependent. Experimentally, a positive correlation between light intensity and activated transducin has been observed at a lower stimulation intensity range, whereas activated transducin starts to decrease at very high intensity light stimulation. Since none of the proposed phototransduction models were able to reproduce the complex characteristics of the signal transduction system of retinal photoreceptor cells, we propose a model that may reproduce the light intensity-dependent amplification of incoming signals in both rods and cones. The present model successfully reproduced the experimental data.
Upon elevation of plasma glucose concentration, pancreatic b-cells generate bursts of action pote... more Upon elevation of plasma glucose concentration, pancreatic b-cells generate bursts of action potentials to induce cyclic changes in [Ca 2＋ ] i regulating insulin release. Glucose-dependent insulin secretion is synergistically enhanced by glucagon-like peptide-1 (GLP-1), which increases [cAMP] i and activates protein kinase A (PKA) and exchange protein activated by cAMP (Epac). The insulinotropic eŠect of GLP-1 is mediated, at least in part, by modulating multiple ion channels/transporters at the plasma membrane and ER through PKA-and EPAC-dependent mechanisms, which increase membrane excitability and intracellular Ca 2＋ release. However, because of complex interactions between multiple cellular factors involved in the GLP-1 eŠects, quantitative aspects of the molecular/ionic mechanisms have not yet been determined. We thus performed simulation studies and mathematical analysis to investigate how GLP-1 signals control [cAMP] i and subsequently modify the bursting activities and Ca 2＋ dynamics. First, a GLP-1 receptor signal transduction model was developed and introduced to our b-cells model. Secondly, modulatory eŠects of PKA/Epac on ion channels/transporters were incorporated based on experimental studies. Increases in the frequency and duration of the bursting activity observed during GLP-1 stimulation were well reconstructed by our model, and lead potential analysis quantitatively determined the functional role of each ion channel/transporter in modifying the burst pattern. Finally, an IP 3 R model was developed to reproduce GLP-1-induced Ca 2＋ transients/oscillations. Instantaneous equilibrium analysis and bifurcation analysis also elucidated the quantitative mechanisms involved in generating IP 3 R-mediated Ca 2＋ mobilization. The results of this theoretical analysis of the eŠects of GLP-1 on membrane excitability/Ca 2＋ dynamics are discussed in this review.
Ca+ sparklets are subcellular Ca2+ signals produced by the opening of L-type Ca2+ channels (LTCCs... more Ca+ sparklets are subcellular Ca2+ signals produced by the opening of L-type Ca2+ channels (LTCCs). In cerebral arterial myocytes, Ca2+ sparklet activity varies regionally, resulting in low and high activity, “persistent” Ca2+ sparklet sites. Although increased Ca2+ influx via LTCCs in arterial myocytes has been implicated in the chain of events contributing to vascular dysfunction during acute hyperglycemia and diabetes, the mechanisms underlying these pathological changes remain unclear. Here, we tested the hypothesis that increased Ca2+ sparklet activity contributes to higher Ca2+ influx in cerebral artery smooth muscle during acute hyperglycemia and in an animal model of non-insulin-dependent, type 2 diabetes: the dB/dB mouse. Consistent with this hypothesis, acute elevation of extracellular glucose from 10 to 20 mM increased the density of low activity and persistent Ca2+ sparklet sites as well as the amplitude of LTCC currents in wild-type cerebral arterial myocytes. Furthermo...
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Papers by Yukari Takeda