HEXOPRENALINE ACTIVATES POTASSIUM CHANNELS OF HUMAN MYOMETRIAL MYOCYTES

Hexoprenaline is a beta-adrenergic agent used for tocolysis after the 26th week of pregnancy. The purpose of the present study was to demonstrate the site of action of hexoprenaline on the membrane of single isolated smooth muscle cells. The main action of beta-mimetics on the cell is hyperpolarization of the cellular membrane, i.e. beta-mimetics have similar effects as K+-ions (Standen et al., 1989). Our results indicate a prolonged and significantly enhanced activity of K+-channels in the cell membrane, as may also be demonstrated by the use of the K+-channel activator Calcitonin-gene related peptide (CGRP). In control experiments under physiological conditions, we observed a large conductance K+-channel with 158 pS. The channel was voltage dependent and Ca++ sensitive indicating that it belongs to the class of big conductance Ca++-activated K+-channels (BK(Ca)). Hexoprenaline and CGRP both increased the open probability (P(o)) of the channel measured with the patch clamp system in the cell attached configuration. Hexoprenaline was also an activator of the BK(Ca) in the presence of Nitrendipine, indicating that the activation of the Ca++ sensitive channel is not an indirect effect of Ca++ currents via L-type Ca++ channels.