POTASSIUM CHANNELS
Presented by: Dr M. Kazevu
Moderator: Dr. D. Kampolo
POTASSIUM CHANNEL STRUCTURE
• Transmembrane proteins highly selective for potassium ions
• Constitute largest and most diverse family of ion channels
• Tetrameric protein with a central pore
• Each subunit contributes to a pore-loop (p-loop) containing a signature
sequence (TVGYG-forms selectivity filter)
• Filter’s carbonyl oxygen mimic coordination geometry of a hydrated
potassium ion allowing rapid dehydration and passage while excluding
smaller ions like sodium
• Gating domains (control opening and closing)
• Voltage sensors
• Ligand binding regions or cytoplasmic extensions
FUNCTION
• Conduct potassium down electrochemical gradient
• Establish and reset RMP
• Shape action potential in excitable cells (neurons, myocytes)
• Regulate cardiac repolarization and vascular tone
• Control hormone secretion (e.g., insulin release from Beta cell)
MAJOR CLASSES
• Calcium-activated potassium channel - open in response to the
presence of calcium ions or other signalling molecules.
• Inwardly rectifying potassium channel - passes current (positive charge)
more easily in the inward direction (into the cell).
• Tandem pore domain potassium channel - are constitutively open or
possess high basal activation, such as the "resting potassium channels"
or "leak channels" that set the negative membrane potential of neurons.
• Voltage-gated potassium channel - are voltage-gated ion channels that
open or close in response to changes in the transmembrane voltage.
MAJOR CLASSES OF POTASSIUM
CHANNEL
CLASS ACTIVATION PRIMARY FUNCTION EXAMPLES
Calcium activated Intracellular calcium or Counteract BK, SK, IK channels
potassium channels ligands depolarization; regulate
(K_Ca) excitability
Inwardly rectifying (Kir) Voltage and intracellular Maintain RMP, Potassium Kir1.1 (ROMK), Kir2.x
blockers recycling in kidneys
Tandem Pore Domain Constitutively open or Constitutively active TREK, TASK, TWIK
(K2P) GPCRs “leak” channels that set
leak conductance;
stabilize membrane
potential
Votltage gated (K_v) Open or close in response Repolarization of action Kv1-Kv12 families
to changes in voltage potentials, limit firing rate
(membrane
depolarization)
PHYSIOLOGICAL AND CLINICAL
SIGNIFICANCE
• By fine-tuning membrane potential and excitability; potassium
channels underlie
• Cardiac rhythm: Mutations in KCNH2 (hERG) or KCNQ1 causes long QT
syndromes and life threatening arrhythmias
• Neuronal signaling: Dysregulation links to epilepsy, ataxias, and neuropathic
pain
• Hormone release: ATP-sensitive Kir6.x channels regulate insulin secretion;
defects lleead to neonatal diabetes or hyperinsulinism
• Toxins e.g., charybdotoxin and pharmacological agents (blockers and
openers) target specific classes.
REFERENCES
• Ashcroft, F.M., 2006. From molecule to malady. Nature, 440(7083), pp.440–447.
• Doyle, D.A., Morais Cabral, J., Pfuetzner, R.A., Kuo, A., Gulbis, J.M., Cohen, S.L., Chait, B.T. and
MacKinnon, R., 1998. The structure of the potassium channel: molecular basis of K⁺ conduction
and selectivity. Science, 280(5360), pp.69–77.
• Hille, B., 2001. Ion channels of excitable membranes. 3rd edn. Sunderland, MA: Sinauer
Associates.
• Jan, L.Y. and Jan, Y.N., 1992. Cloned potassium channels from eukaryotes and prokaryotes. Annual
Review of Neuroscience, 15, pp.91–123.
• MacKinnon, R., 2003. Potassium channels and the atomic basis of selective ion conduction.
Angewandte Chemie International Edition, 42(40), pp.4714–4721.
• Sanguinetti, M.C. and Tristani-Firouzi, M., 2006. hERG potassium channels and cardiac
arrhythmia. Nature, 440(7083), pp.463–469.
• Yellen, G., 2002. The voltage-gated potassium channels and their relatives. Nature, 419(6902),
pp.35–42.
THANK
YOU
