The excitatory effect of hydrogen sulfide on rat colonic muscle contraction and the underlying mechanism

H₂S is a well-known relaxant regulator in muscle contraction but little attention has been paid to its excitatory effect on colonic motility. To investigate the excitation of H₂S on rat colonic contraction and the underlying mechanism, the muscle contractile activity was assessed by an organ bath system, the level of substance P (SP) in the colon was detected using enzyme immunoassay kits, L-type Ca²⁺ channel currents (I_Ca,L) and large conductance Ca²⁺-activated K⁺ channel currents (I_BK) in smooth muscle cells (SMCs) were measured by patch-clamp electrophysiology. The results show that the H₂S donor NaHS (100 μM) reversed the relaxation of the NO donor SNP on colonic muscle contraction. Pretreatment with the TRPV1 antagonist and the neurokinin receptor antagonists attenuated the NaHS-induced excitation. Incubation of colon with NaHS increased the SP level. In freshly isolated SMCs, NaHS exerted a biphasic effect on I_Ca,L and concentration-dependently inhibited the I_BK. And 100 μM NaHS partially reversed the SNP-induced changes in I_Ca,L and I_BK. We concluded that exogenous H₂S exerts a potential excitatory effect on colonic motility, which may be achieved by activating SP release from afferent nerves in combination with a direct activation of I_Ca,L and suppression of I_BK in SMCs.