MODULATION OF CALCIUM CURRENTS BY G-PROTEINS AND ADENOSINE RECEPTORS IN MYENTERIC NEURONS CULTURED FROM ADULT GUINEA-PIG SMALL-INTESTINE

1 Whole-cell patch clamp methods were used to analyse voltage-dependent calcium currents in cultured myenteric neurones enzymatically isolated from adult guinea-pig small intestine. 2 Activation of G-proteins by intracellular administration of GTP-gamma-S (100-200 mu M in pipette) decreased the amplitude of high voltage activated Ca2+ current (I-Ca) by more than 50%. Residual I-Ca was activated more slowly and was non-inactivating during 500 ms test pulses when GTP-gamma-S was included in the pipette solution. 3 Inclusion of 500 mu M GDP-B-S in the patch pipettes increased the amplitude of I-Ca by over 30% without altering the voltage-dependency. 4 Extracellular application of 2-chloroadenosine suppressed I-Ca dose-dependently by reducing both transient and sustained components of the current. 5 Pretreatment of the neurones with cholera toxin or forskolin did not alter the actions of GTP-gamma-S or GDP-beta-S or 2-chloroadenosine. 6 The results suggest that high threshold calcium channels in myenteric neurones are influenced by G-proteins and that the inhibitory action of 2-chloroadenosine on I-Ca involves G-protein coupling of the adenosine receptors to the Ca2+ channel.