Effect of Hydrogen Sulphide on Spontaneous Contractions of the Rat Jejunum. Role of K_V-, K_Ca-, and K_ir-Channels

Abstract

In this work, we analyzed the role of voltage-gated (KV), calcium-activated (KCa), and inward-rectifier potassium channels (Kir) in the effects of hydrogen sulphide (H2S) donor sodium hydrosulphide (NaHS) on the spontaneous contractile activity of the rat jejunum. Experiments were performed on jejunum segments under isometric contraction conditions. It was shown that NaHS reduced the basal tension of the segments, the amplitude, and the frequency of spontaneous contractions in a dose-dependent manner (10–500 μM); the half-effective concentration (EC50) of the inhibitory effect of NaHS on amplitude was 165 μM. The KV channel blocker 4-AP (200 µM) increased the amplitude of spontaneous contractions and subsequent application of NaHS (200 μM) suppressed the amplitude and frequency of spontaneous activity as well as in the control; the effect on tonic tension was less pronounced. TEA (3 mM), a non-specific blocker, and paxillin (1 µM), a specific blocker of large conductance KСа (ВK) channels, increased the amplitude of spontaneous contractions, while the inhibitory effect of NaHS was completely preserved. The selective blocker of small conductance KCa (SK) channels NS8593 (4 μM) did not affect the tension and the parameters of spontaneous contractions and did not prevent the effects of NaHS. Diazoxide (100 μM), the opener of КATP channels, caused a decrease in the basal tone, the amplitude and frequency of spontaneous contractions. Diazoxide and KATP channel blocker glibenclamide (50 μM) prevented the effects of NaHS on the basal tone. The Kir-channel blocker BaCl2 (30 µM) increased the amplitude of spontaneous contractions and eliminated the inhibitory effects of NaHS on the frequency and amplitude of spontaneous contractions, and the basal tension decrease was less pronounced compared to control. Thus, a decrease in the tonic tension of a rat jejunum preparation under the action of an H2S donor is associated with the activation of Kir, including КATP channels, while the effects of H2S on the amplitude and frequency of spontaneous contractions are mediated by an increase in Ba2+-sensitive conductance.