Galanin suppresses calcium conductance and activates inwardly rectifying potassium channels in myenteric neurones from guinea-pig small intestine

Whole-cell patch-clamp recording methods were used to investigate the ionic mechanisms underlying the hyperpolarizing action of galanin in enteric neu rones. Galanin suppressed calcium current (I-Ca) and activated inwardly rec tifying potassium current (I-K,I-ir) in AH-type myenteric neurones of guine a-pig small intestine. Both suppression of I-Ca and activation of I-K,I-ir were concentration-dependent, with an EC50 of 1.4 nmol L-1 and 55 nmol L-1, respectively. Pretreatment with pertussis toxin eliminated both actions of galanin, suggesting that both galanin-induced inhibition of I-Ca and galan in-induced activation of I-K,I-ir involved activation of G(i)/G(o) proteins . Both suppression of I-Ca and activation of I-K,I-ir by galanin were mimic ked by the N-terminal fragment of galanin, galanin-(1-16) suggesting that t he first 16 amino acids of the peptide were sufficient for both actions. Th e galanin receptor antagonist galantide suppressed the galanin-induced acti vation of I-K,I-ir with an EC50 of 16 nmol L-1. However, galantide alone su ppressed I-Ca. The results suggest two mechanisms of action for galanin: on e is opening of inwardly rectifying potassium channels and the second is bl ockade of voltage-activated calcium channels.