In this study we investigated the role of voltage dependent (K V ), Ca 2+ -activated (K Ca ), and inward rectifier (K ir ) potassium channels in the effects of hydrogen sulfide donor (H 2 S) 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 (EC 50 ) 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. BaCl 2 , 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 H 2 S donor was associated with activation of K ir channels, including K ATP channels, whereas the effect of H 2 S on amplitude and frequency was mediated by an increase in Ba 2+ -sensitive conductivity.

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.

Эксперименты проводили на мышах возрастом 45 дней, где в опытной группе СРК индуцировали путем неонатальной сенсибилизации. Оценивали силу сокращения сегментов проксимального отдела толстой кишки мыши в изометрических условиях и оказалось, что у мышей с моделью СРК повышена амплитуда сокращений. Применение бутирата натрия приводило к значительному снижению амплитуды сокращений препарата, однако данные эффекты были менее выражены в опытной группе. L-NAME в контрольной группе приводило к повышению амплитуды, а в модели СРК напротив добавление L-NAME не приводило к достоверным изменениям параметров сокращения. При этом в обеих исследуемых группах угнетающее действие бутирата натрия на параметры сократимости на фоне аппликации L-NAME были выражены в меньшей степени чем в контроле. Ключевые слова: синдром раздраженного кишечника, короткоцепочечные жирные кислоты, оксид азота, сократимость, толстая кишка.