The contribution of Rb‐permeable potassium channels to the relaxant and membrane hyperpolarizing actions of cromakalim, RP49356 and diazoxide in bovine tracheal smooth muscle

Abstract

1. Cromakalim (1 and 10 microM), RP49356 (5 and 50 microM) and diazoxide (100 and 300 microM) produced full relaxation of smooth muscle strips pre-contracted with 25 mM KCl. These agents caused membrane hyperpolarization and increased 42K and 86Rb efflux. The time taken to achieve the maximum change in each of these parameters (tmax) 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 cormakalim (1 and 10 microM) produced a greater rise in PK than PRb, although the PRb:PK ratio was similar 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 microM) and was reflected by a differential effect of the two concentrations of RP49356 on the PRb:PK ratio. Diazoxide (100 and 300 microM) produced similar changes in PK and PRb. 3. For cromakalim (1 and 10 microM) the tmax 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 microM), changes in tension and membrane potential were related to both changes in PK and PRb, whereas at 50 microM these responses more closely corresponded to changes in PK. For diazoxide (100 and 300 microM) the electrical and mechanical effects corresponded to changes in both PK and PRb. 4. The results show that changes in 42K and 86Rb 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.