Key result
Acidosis increases C-type inactivation of Kv1.4 K+ channels, an effect abolished by mutating pore residues.
Why the study?
The mechanism by which acidosis enhances C-type inactivation of the Kv1.4 K+ channel was not fully understood.
The study identifies specific pore residues (H508 and K532) that mediate the acidosis-induced enhancement of C-type inactivation in Kv1.4 potassium channels.
Basic Kv1.4 pH sensitivity mechanism shown in oocytes; leaves open relevance to cardiac electrophysiology or arrhythmias.
Acidosis inhibits current through the Kv1.4 K(+) channel, perhaps as a result of enhancement of C-type inactivation. The mechanism of action of acidosis on C-type inactivation has been studied. A mutant Kv1.4 channel that lacks N-type inactivation (fKv1.4 Delta2-146) was expressed in Xenopus oocytes, and currents were recorded using two-microelectrode voltage clamp. Acidosis increased fKv1.4 Delta2-146 C-type inactivation. Replacement of a pore histidine with cysteine (H508C) abolished the increase. Application of positively charged thiol-specific methanethiosulfonate to fKv1.4 Delta2-146 H508C increased C-type inactivation, mimicking the effect of acidosis. Replacement of a pore lysine with cysteine (K532C) abolished the acidosis-induced increase of C-type inactivation. A model of the Kv1.4 pore, based on the crystal structure of KcsA, shows that H508 and K532 lie close together. It is suggested that the acidosis-induced increase of C-type inactivation involves the charge on H508 and K532.
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Claydon et al. (2002) studied Acidosis effect on Kv1.4 K+ channel. Acidosis and pore residue mutations (H508C, K532C) was evaluated on C-type inactivation of the Kv1.4 K+ channel. Acidosis increased C-type inactivation of the Kv1.4 K+ channel, an effect that was abolished by replacing pore residues H508 or K532 with cysteine.
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