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Temperature dependence of drug blockade of a calcium-dependent potassium channel in cultured hippocampal neurons.

Abstract：

:The temperature dependence of drug blockade of a calcium-dependent potassium channel K(Ca) has been studied in cultured CA1 hippocampal neurons. Channel openings from a 70-pS K+ channel were recorded when inside-out patches were exposed to a bath solution containing 140 mM K+ and 0.2 mM Ca2+. The mean open times of channel events were not significantly altered when the bath temperature was lowered from 24 degrees to 14 degrees C (Q10 = 1.2). Introduction of the drug RP-62719 into the bath solution (at 5 microM) resulted in the mean open time of the K(Ca) channel to be diminished by 85% (at 24 degrees C) with no change in the amplitudes of the unitary currents. Over the same temperature range of 24 degrees to 14 degrees C, in the presence of RP-62719, the mean open times were significantly prolonged (Q10 = 2.2). A simple open channel block scheme was used to determine the temperature dependence of the onward- (blocking) and off- (unblocking) rate constants. Thermodynamic analysis, using transition rate theory, showed that the blocking rate constant was associated with a large increase in entropy. The relatively high temperature dependence for channel blockade is not consistent with a rate-limiting process established by simple diffusion of the agent to a channel blocking site. Channel block may involve conformational changes in the channel protein as a consequence of hydrophobic interactions between drug and channel sites.

journal_name

Biophys J

journal_title

Biophysical journal

authors

McLarnon JG,Wang XP

doi

10.1016/S0006-3495(91)82161-0

subject

Has Abstract

pub_date

1991-11-01 00:00:00

pages

1278-87

issue

5

eissn

0006-3495

issn

1542-0086

pii

S0006-3495(91)82161-0

journal_volume

60

pub_type

杂志文章

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