Differential effects of elevating [K]o on three transient outward potassium channels. Dependence on channel inactivation mechanisms.

Abstract:

:We carried out a systematic study on the effects of elevating [K]o on the properties of a transient outward potassium channel encoded by a cardiac cDNA (RHK1) and compared them with those on two Shaker potassium channels (H-4 and H-37). The amino acid sequences of all three channels are known, and their structure-function relations have been partially characterized. All three channels were expressed in Xenopus oocytes and studied under double-microelectrode voltage-clamp conditions. For all three channels, elevating [K]o caused an increase in the channels' chord conductances and a negative shift in the calculated activation curves. However, in other aspects of channel properties that are related to the channels' inactivation processes, there were differences in the changes induced by increasing [K]o: 1) Elevating [K]o caused a positive shift in the steady-state inactivation curves of RHK1 and H-4 but did not cause any shift in H-37. 2) Elevating [K]o slowed the time course of inactivation of H-37 but did not cause any significant changes in the time course of RHK1 or H-4. 3) Elevating [K]o accelerated the rate of recovery from inactivation of RHK1 and H-4 but slowed the recovery time course of H-37. Our experiments show that elevating [K]o can cause a wide range of effects on the transient outward potassium channels. Furthermore, raising [K]o induced similar changes in RHK1 and H-4 (inactivation mediated by an "N-type" mechanism) that were different from the changes in H-37 (inactivation mediated by a "C-type" mechanism). Therefore, our data suggest that part of the effects of elevating [K]o on channel properties may depend on the channel's inactivation mechanism. This hypothesis is supported by results from experiments studying the effects of elevating [K]o on a mutant RHK1 channel (RHK1 delta 3-25), which apparently lacks the N-type and C-type inactivation mechanisms.

journal_name

Circ Res

journal_title

Circulation research

authors

Tseng GN,Tseng-Crank J

doi

10.1161/01.res.71.3.657

subject

Has Abstract

pub_date

1992-09-01 00:00:00

pages

657-72

issue

3

eissn

0009-7330

issn

1524-4571

journal_volume

71

pub_type

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