Modulation of calcium currents by G-proteins and adenosine receptors in myenteric neurones 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 microM in pipette) decreased the amplitude of high voltage activated Ca2+ current (ICa) by more than 50%. Residual ICa 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 microM GDP-beta-S in the patch pipettes increased the amplitude of ICa by over 30% without altering the voltage-dependency. 4. Extracellular application of 2-chloroadenosine suppressed ICa 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 ICa involves G-protein coupling of the adenosine receptors to the Ca2+ channel.