Effects of forskolin on electrical behaviour of myenteric neurones in guinea-pig small intestine.

The actions of forskolin on electrical behaviour of myenteric neurones were investigated with intracellular recording methods in guinea-pig small intestine. The actions of forskolin were: membrane depolarization, increased input resistance, suppression of post-spike hyperpolarizing potentials and repetitive spike discharge. These effects occurred always in AH/Type 2 myenteric neurones and never in the cells classified as S/Type 1. Reversal potentials for the depolarizing effects were near the estimated potassium equilibrium potential. Analyses based on the 'constant field equation' indicated that the permeability ratios of K+ to other permeant ionic species were reduced by forskolin. Pretreatment of the neurones with a phosphodiesterase inhibitor potentiated the effects of forskolin. The results suggest that activation of adenylate cyclase by forskolin and subsequent elevation of intraneuronal adenosine 3',5'-phosphate (cyclic AMP) mimic slow synaptic excitation in AH/Type 2 myenteric neurones. They support the possibility that cyclic AMP functions as a second messenger in signal transduction which appears to involve closure of calcium-dependent K+ channels and other membrane changes that lead to depolarization and a dramatic increase in the excitability of the neurones.