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.
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D005576:Colforsin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000294:innervation; D008274:Magnesium / Q000494:pharmacology; D009130:Muscle, Smooth / Q000294:innervation*; D009197:Myenteric Plexus / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000187:drug effects*; D011188:Potassium / Q000494:pharmacology; D013569:Synapses / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D013997:Time Factors
D005576:Colforsin; D013779:Tetrodotoxin; D008274:Magnesium; D011188:Potassium; D015056:1-Methyl-3-isobutylxanthine