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Inhibition of delayed rectifier K + ‐current by levcromakalim in single intestinal smooth muscle cells: effects of cations and dependence on K + ‐flux
Author(s) -
McHugh D.,
Beech D J.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb13239.x
Subject(s) - depolarization , chemistry , patch clamp , biophysics , analytical chemistry (journal) , biochemistry , biology , chromatography , receptor
1 Whole‐cell voltage‐clamp recordings were made from single smooth muscle cells isolated from the longitudinal layer of the guinea‐pig small intestine. 2 Levcromakalim ((−)Ckm) inhibited delayed rectifier K‐current ( I K(DR) ) and induced a voltage‐independent K‐current ( I K(‐Ckm) ). Both effects were inhibited similarly by glibenclamide. In some cells, however, I K(‐ckm) could be induced without any effect on I K(DR) . 3 Ba 2+ caused a voltage‐dependent block of I K(‐Ckm) . The IC 50 was 0.2 m m at − 40 mV (6 cells), but at 0 mV 2 m m Ba 2+ caused only a 26 ± 7% inhibition ( n = 5). Ba 2+ had much less effect on I K(DR) , 2 m m Ba 2+ having no inhibitory effect on current elicited by depolarization to − 30 mV ( n = 6) or 0 mV ( n = 5). 4 Low concentrations of Zn 2+ blocked I K(‐Ckm) while having little effect on I K(DR) . Zn 2+ (40 μ m ) caused a 77 ± 1% reduction of I K(‐Ckm) at − 30 mV ( n = 4) but I K(DR) was inhibited by only 10 ± 3% at the same voltage ( n = 4). 5 Inward current amplitudes were compared in 135 m m Rb + and 135 m m K + bath solutions. (−)Ckm‐activated Rb + ‐current was only 4% of the K + ‐current, whereas delayed rectifier Rb + ‐current was larger than K + ‐current. 6 (−)Ckm did not inhibit I K(DR) if I K (‐Ckm) was blocked. In the presence of 2 m m Ba 2+ or 135 m m Rb + , (−)Ckm did not induce current nor did it inhibit the delayed rectifier. When [Rb + ] o was 25 m m and [K + ] i was 130 m m , (−)Ckm elicited outward current and inhibited outward delayed rectifier current (at voltages positive of the reversal potential) but it did not elicit inward current or inhibit inward delayed rectifier current (at voltages negative of the reversal potential). 7 These experiments indicate that (−)Ckm‐activated K channels are more sensitive to inhibition by Ba 2+ and Zn 2+ and pass inward Rb + current less well than delayed rectifier K channels. They also suggest that (−)Ckm does not modulate delayed rectifier K channels directly or via an intermediate protein but that the inhibitory effect of (−)Ckm on I K(DR) arises as a consequence of K + ‐flux through (−)Ckm‐activated K channels.