Suppressive effect of an activator of ATP-dependent potassium channels, flocalin, on electrical and contractile activities of smooth muscles of the guinea-pig ureter

Abstract

In experiments on isolated segments or strips obtained from the guinea-pig ureter, we showed, using a sucrosegap technique, that application of an activator of ATP-dependent potassium channels (K ATP ), flocalin (PF-5), suppresses generation of action potentials (APs) by ureter smooth muscle cells (SMCs). Pre-incubation of the ureter preparations under study in Krebs solution containing 1 to 10 μM PF-5 results initially in a decrease in the frequency of oscillations preceding an AP plateau, shortening of this plateau, and, later on, complete inhibition of AP generation. In the presence of PF-5, spikes induced by hyperpotassium depolarization were also inhibited, while a tonic component of such depolarization underwent a mild decrease. The data obtained indicate that PF-5 modulates the entry of Са 2+ ions through L-type voltage-dependent channels in the SMC membrane. Shortening of the plateau and suppression of the spikes initiated by application of an activator of voltage-dependent L-type potassium channels, Вау K 8644, can be considered a confirmation of the modulatory influence of PF-5 on voltage-dependent L-type potassium channels. It seems possible that Вау K 8644 can be used under experimental conditions for initiation and long-lasting modulation of APs generated by the ureter SMC instead of corresponding neurotransmitters. We hypothesize that voltage-dependent entry of Са 2+ ions into SMCs depends significantly on the PF-5-induced activation of K ATP channels of the ureter SMCs.

Effects of fluorine-containing opener of ATP-sensitive potassium channels, pinacidil-derivative flocalin, on cardiac voltage-gated sodium and calcium channels

“…Moreover, flocalin also potently reduced the amplitude of [Ca 2+ ] i transients in isolated cardiomyocytes during the AP (Voitychuk et al 2011), which provided additional argument in favor of its action on L-type VGCCs. Indirect evidence on L-type VGCC inhibition by flocalin was also obtained in the smooth muscle strips of the guinea pig ureter (Yanchii et al 2005).…”