Galanin Activates an Inwardly Rectifying Potassium Conductance and Inhibits a Voltage‐Dependent Calcium Conductance in Mudpuppy Parasympathetic Neurons a

A bstract : Galanin‐induced activation of an inwardly rectifying membrane potassium (K + ) current and inhibition of barium current (I Ba ) were studied using whole cell voltage clamp recording techniques in parasympathetic neurons dissociated from the mudpuppy cardiac ganglion. Both activation of the K + current and inhibition of I Ba were concentration‐dependent with an EC 50 (or IC 50 ) of ˜35 nM and ˜0.4 nM, respectively. Both actions of galanin were eliminated by pretreatment with pertussis toxin, which suggested involvement of G i /G o protein activation. Galantide antagonized the galanin‐induced activation of K + current with an IC 50 equal to 4 nM. By contrast, galantide, by itself, inhibited I Ba with an EC 50 equal to 16 nM. Another galanin analog, M40, primarily antagonized the galanin‐induced activation of K + current, but in some cells, M40 also acted as a weak agonist. M40, like galantide, inhibited I Ba . The NH 2 ‐terminal fragment galanin‐(1–16) activated the K + current and inhibited I Ba , indicating that the first 16 amino acids of the galanin peptide were sufficient for both actions. In summary, it is postulated that the effects of galanin on mudpuppy parasympathetic neurons might be mediated by activation of two different subtypes of galanin receptor, one that regulates membrane K + conductance and a second that modulates calcium conductance.