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The contribution of Rb‐permeable potassium channels to the relaxant and membrane hyperpolarizing actions of cromakalim, RP49356 and diazoxide in bovine tracheal smooth muscle
Author(s) -
Longmore J.,
Bray K.M.,
Weston A.H.
Publication year - 1991
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.1476-5381.1991.tb12287.x
Subject(s) - cromakalim , diazoxide , chemistry , hyperpolarization (physics) , membrane potential , potassium channel opener , potassium channel , medicine , endocrinology , potassium , muscle contraction , biophysics , biochemistry , biology , stereochemistry , agonist , receptor , organic chemistry , nuclear magnetic resonance spectroscopy , insulin
1 Cromakalim (1 and 10 μ m ), RP49356 (5 and 50 μ m ) and diazoxide (100 and 300 μ m ) produced full relaxation of smooth muscle strips pre‐contracted with 25 m m KCl. These agents caused membrane hyperpolarization and increased 42 K and 86 Rb efflux. The time taken to achieve the maximum change in each of these parameters ( t max ) was less for the higher concentration levels of cromakalim, RP49356 and diazoxide than for the lower concentration levels. 2 Calculation of permeability (P) changes showed that cromakalim (1 and 10 μ m ) produced a greater rise in PK than PRb, although the PRb:PK ratio was simiiar at both concentration levels. Similarly RP49356 produced a greater change in PK than PRb. However, in contrast to cromakalim, this difference was more marked at the higher concentration (50 μ m ) and was reflected by a differential effect of the two concentrations of RP49356 on the PRb:PK ratio. Diazoxide (100 and 300 μ m ) produced similar changes in PK and PRb. 3 For cromakalim (1 and 10 μ m ) the t max for the electrical and mechanical effects and also the profile of change in these parameters corresponded to changes in both PK and PRb. For RP49356 (5 μ m ), changes in tension and membrane potential were related to both changes in PK and PRb, whereas at 50 μ m these responses more closely corresponded to changes in PK. For diazoxide (100 and 300 μ m ) the electrical and mechanical effects corresponded to changes in both PK and PRb. 4 The results show that changes in 42 K and 86 Rb efflux induced by cromakalim, RP49356 and diazoxide are good indicators of changes in membrane PK and PRb evoked by these agents. Furthermore, it is concluded that the K channels involved in the mechanical and electrical effects of cromakalim are represented by the opening of a single population through which Rb can pass less easily than K, whilst the K channels associated with actions of diazoxide are equally permeable to both K and Rb. In contrast, the relaxant and membrane hyperpolarizing actions of RP49356 may involve the opening of more than one group of K channels which differ in their permeability to Rb.