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.
