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 neurones. Galanin suppressed calcium current (ICa) and activated inwardly rectifying potassium current (IK,ir) in AH-type myenteric neurones of guinea-pig small intestine. Both suppression of ICa and activation of IK,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 ICa and galanin-induced activation of IK,ir involved activation of Gi/Go proteins. Both suppression of ICa and activation of IK,ir by galanin were mimicked by the N-terminal fragment of galanin, galanin-(1-16) suggesting that the first 16 amino acids of the peptide were sufficient for both actions. The galanin receptor antagonist galantide suppressed the galanin-induced activation of IK,ir with an EC50 of 16 nmol L-1. However, galantide alone suppressed ICa. The results suggest two mechanisms of action for galanin: one is opening of inwardly rectifying potassium channels and the second is blockade of voltage-activated calcium channels.
Ren
J
J
Department of Physiology and Cell Biology, College of Medicine and Public Health, Ohio State University, OH 43210-1218, USA.
Hu
H Z
HZ
Starodub
A M
AM
Wood
J D
JD
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002772:Cholera Toxin / Q000494:pharmacology; D019004:Galanin / Q000494:pharmacology*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000294:innervation / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009197:Myenteric Plexus / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D015221:Potassium Channels / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D010566:Virulence Factors, Bordetella; D019004:Galanin; D002772:Cholera Toxin; D037342:Pertussis Toxin; D002118:Calcium