Electrophysiological Properties of Gastric Pacemaker Potentials

Abstract

Electrophysiological properties of pacemaker potentials recorded from myenteric interstitial cells of Cajal (ICC-MY) within the guinea-pig gastric antrum are reviewed briefly. Pacemaker potentials consist of two components, a primary component forming a transient depolarization with a rapidly rising initial phase, followed by a secondary component as a plateau with sustained depolarization. The primary component is inhibited by low [Ca²⁺]_o solutions or depolarization of the membrane with high [K⁺]_o solutions. This inhibition could be mimicked by chelating [Ca²⁺] _i with BAPTA-AM, suggesting that this component is produced by activation of voltage-dependent Ca²⁺ permeable channels. The plateau component is inhibited by low [Cl^-] _o solution or DIDS, an inhibitor of Ca²⁺-activated Cl^--channels, suggesting that this component is formed by Ca²⁺-activated Cl^--currents. Reduction of Ca²⁺ release from internal stores by inhibiting the internal Ca-pump with cyclopiazonic acid results in a shortened duration of the plateau component, with no alteration in the rate of rise of the primary component. 2-APB, an inhibitor of the IP₃-receptor mediated Ca²⁺ release from internal stores, abolishes pacemaker potentials, suggesting that the release of Ca²⁺ from internal IP₃-sensitive Ca²⁺ stores is required for generation of pacemaker potentials. CCCP, a mitochondrial protonophore, depolarizes the membrane and abolishes pacemaker potentials, suggesting that mitochondrial Ca²⁺ handling functions may be coupled with generation of pacemaker potentials. These results indicate that the two components of pacemaker potentials are generated by different mechanisms; the primary component may be produced by activation of voltage-dependent Ca²⁺-permeable channels, while the plateau component may be produced by the opening of Ca²⁺-activated Cl^--channels. It is hypothesized that pacemaker potentials are initiated by depolarization of the membrane due to generation of unitary potentials in response to mitochondrial Ca²⁺ handling. Activation of voltage-dependent Ca²⁺ influx, IP₃-receptor mediated Ca²⁺ release from the internal stores and Ca²⁺-activated Cl^--channels may be involved as successive steps downstream to the generation of unitary potentials.