Role of intracellular stored calcium on the generation of spontaneous activity in gastrointestinal smooth muscle

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Recording of electrical responses from the isolated stomach muscles of the guinea-pig produced periodical generation of slow potentials with about 30 mV in amplitude and 5-6 s in duration. Slow potentials were not inhibited by TTX or Ca antagonists. Slow potentials were abolished by DIDS or niflumic acid, suggested that the potentials were produced by activation of Ca-sensitive Cl channels. Measurement of intracellular Ca concentrations by using Ca-indicator fula-2 fluorescence indicated that slow potentials were associated with an increase in intracellular Ca concentrations. Ca-responses, together with slow potentials, were inhibited by BAPTA (an intracellular Ca chilator), 2-APB (an inhibitor of IP3 receptors) and CPA (an inhibitor of internal Ca-pump). Inhibitors of mitochondrial protonophore (CCCP) or mitochondrial ATP-sensitive K-channel (5-HDA) also abolished the generation of slow potentials and Ca-transients. These results suggested that mitochondrial activity produced as a results of proton production induces an activation of Ca-sensitive enzymes and finally produces IP3, which in tern elevates intracellular Ca concentrations by releasing from the internal stores and activates Ca-sensitive ion channels at the plasma membrane. These processes are considered involved in the generation of pacemaker potentials in gastric pacemaker cells.