GABAB receptors are required for galanin modulation of membrane properties of neurons in the arcuate nucleus of rats.
Galanin-mediated modulation of the arcuate nucleus (Arc) neurons is thought to be involved in the regulation of feeding behavior, hormone secretion, and reproduction. We previously reported that galanin perfusion significantly hyperpolarized the resting membrane potential and suppressed the spontaneous firing in the Arc neurons in slice preparation. In this study, we focused on the cellular and molecular mechanisms underlying the galanin effect. The galanin action is mediated by the galanin receptors (GAL1/2/3R). We found that activation of galanin receptors alone is not sufficient to mediate the galanin effect on resting membrane potential and spontaneous firing; co-activation of GABA(B) receptors is required for galanin to accomplish its modulation on the membrane properties of Arc neurons. In more details, the effect of galanin on the membrane properties of Arc neurons is blocked by either lowering the extracellular Ca(2+) or the inhibition of GABA(B) receptors with the selective GABA(B) antagonist, saclofen. In addition, activation of GABA(B) receptors by baclofen restored the galanin effect under low Ca (2+) conditions. These results suggest that GABA(B) receptors may serve as a molecular gate for galanin signaling, and thus can be targeted to manipulate the galanin-mediated physiological and behavioral responses.
Tyszkiewicz
Joanna P
JP
Merck Research Laboratories, PO Box 2000, R80M-213, Rahway, NJ 07065, USA. joanna_tyszkiewicz@merck.com
Fong
Tung M
TM
Dong
Yan
Y
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D005260:Female; D019004:Galanin / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000378:metabolism*; D044088:Receptors, Galanin / Q000502:physiology
D018080:Receptors, GABA-B; D044088:Receptors, Galanin; D019004:Galanin; D002118:Calcium