Polyamine Block of Inwardly Rectifying Potassium (Kir) Channels
Inwardly rectifying potassium (Kir) channels were first identified based on their unique functional property of preferential conductance of potassium ions into the cell. The property of inward rectification differs significantly from their more widely studied Kv (voltage-gated potassium) channel relatives, which exhibit outward rectification resulting from voltage-dependent opening and closing of the channel pore. Rather, inward rectification arises from asymmetrical voltage-dependent blockade of these channels by endogenous intracellular polyamines. This distinct role of polyamines enables the physiological function of Kir channels to maintain a substantial potassium conductance when cells are at rest, but to shut down their conductance when faced with depolarizing stimuli to allow excitation events (e.g., action potentials) to take place. Functional studies of cloned Kir channels, and recent crystallographic insights, have revealed the importance of numerous side chains that line the channel and interact with polyamines as they move toward a stable binding site. The displacement of permeating K+ ions in the channel pore, coupled to polyamine migration through the pore, underlies the very steeply voltage-dependent blockade.
KeywordsAndersen’s syndrome Electrophysiology Inward rectifier Ion channel Long QT Polyamine Potassium channel Short QT Spermine
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