Effect of Hydrogen Sulphide on Spontaneous Contractions of the Rat Jejunum: Role of KV, KCa, and Kir Channels

Abstract

In this study we investigated the role of voltage dependent (K_V), Ca²⁺-activated (K_Ca), and inward rectifier (K_ir) potassium channels in the effects of hydrogen sulfide donor (H₂S) sodium hydrosulfide (NaHS) on spontaneous contractile activity of rat jejunum. It was shown that NaHS dose-dependently (10–500 μM) reduced the tonus of the preparation, as well as the amplitude and frequency of spontaneous contractions of jejunum preparations under isometric conditions; the half-maximal effective concentration (EC₅₀) of the inhibitory effect of NaHS on the amplitude of contractions was 165 μM. The blocker of K_V channels 4-AP (200 μM) caused an increase in the amplitude of spontaneous contractions. NaHS (200 μM) decreased the amplitude and frequency of spontaneous activity of the preparation in the presence of 4-AP as well as in the control, and the effect on basal tonus was less pronounced. Blockers of large conductance K_Ca channels (BK), non-specific TEA (3 mM) and specific paxillin (1 μM), increased the amplitude of spontaneous contractions, while the depressing effect of NaHS was completely preserved. The selective blocker of small conductance K_Ca channels (SK) NS8593 (4 μM) did not affect the tonus of the preparation and the parameters of spontaneous contractions; it did not prevent the effect of NaHS. The activator of K_ATP channels diazoxide (100 μM) caused a decrease in the basal tonus of the preparation, as well as the amplitude and frequency of spontaneous contractions. Diazoxide and the K_ATP channel blocker glibenclamide (50 μM) prevented the effect of NaHS on the tonus of the preparation. BaCl₂, the K_ir channel blocker (30 μM), caused an increase in the amplitude of spontaneous contractions and prevented the development of the NaHS inhibitory effects on the frequency and amplitude of spontaneous contractions; the decrease in tonus was less pronounced than in the control. Thus, a decrease in the basal tonus of the rat jejunum preparation under the action of the H₂S donor was associated with activation of K_ir channels, including K_ATP channels, whereas the effect of H₂S on amplitude and frequency was mediated by an increase in Ba²⁺-sensitive conductivity.