Journal
JOURNAL OF GENERAL PHYSIOLOGY
Volume 116, Issue 4, Pages 561-568Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1085/jgp.116.4.561
Keywords
inward-rectifier K+ channel; channel block; ion permeation; polyamines; HEPES
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Funding
- NHLBI NIH HHS [HL03814] Funding Source: Medline
- NIGMS NIH HHS [R01 GM055560, GM55560] Funding Source: Medline
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The IRK1 channel is inhibited by intracellular cations such as Mg2+ and polyamines in a voltage-dependent manner, which renders its I-V curve strongly inwardly rectifying. However, even in excised patches exhaustively perfused with a commonly used artificial intracellular solution nominally free of Mg2+ and polyamines, the macroscopic I-V curve of the channels displays modest rectification. This observation forms the basis of a hypothesis, alternative to the pore-blocking hypothesis, that inward rectification reflects the enhancement of intrinsic channel gating by intracellular cations. We find, however, that residual rectification is caused primarily by the commonly used pH buffer HEPES and/or some accompanying impurity. Therefore, inward rectification in the strong rectifier IRK1, as in the weak rectifier ROMK1, can be accounted for by voltage-dependent block of its ion conduction pore by intracellular cations.
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