Galanin inhibits a dihydropyridine-sensitive Ca2+ current in the RINm5f cell line.
Mechanisms of action of the neuropeptide galanin, a putative neuromodulator in the central and peripheral nervous systems, have been evaluated extensively in insulin-secreting cells isolated from pancreas and cell lines derived from pancreatic tumors. Galanin inhibits insulin secretion from these cells through several mechanisms, including activation of ATP-dependent K+ channels and inhibition of adenylyl cyclase leading to a decrease in cAMP. Here we report that galanin also inhibits a dihydropyridine-sensitive Ca2+ current. Both electrophysiological actions by galanin would result in less Ca2+ entry, as the action to increase K+ current would hyperpolarize the cells and the decrease in voltage-gated Ca2+ current would decrease Ca2+ influx at depolarized potentials where these channels are activated. These galanin actions would directly counter the two opposing electrophysiological responses to carbohydrate stimulation in RINm5f cells, which are to inhibit K+ current and to stimulate Ca2+ current. Given that stimulation of presynaptic nerve terminals in pancreas releases galanin, these results suggest that Ca(2+)-dependent insulin release from native pancreatic beta cells may also be regulated by similar neuropeptide effects.
Homaidan
F R
FR
Department of Pharmacology, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853.
Sharp
G W
GW
Nowak
L M
LM
D000818:Animals; D002118:Calcium / Q000502:physiology*; D015220:Calcium Channels / Q000187:drug effects*; D004095:Dihydropyridines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004553:Electric Conductivity; D019004:Galanin; D066298:In Vitro Techniques; D007340:Insulinoma / Q000503:physiopathology; D007515:Islets of Langerhans / Q000502:physiology*; D008564:Membrane Potentials; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; D004095:Dihydropyridines; D010455:Peptides; C038806:1,4-dihydropyridine; D019004:Galanin; D002118:Calcium