Mechanism of action of galanin on myenteric neurons.
1. Conventional intracellular recording methods were used to investigate the mechanism of action of galanin on electrical behavior of AH/type 2 myenteric neurons in the guinea pig small intestine. 2. The overall action of galanin was inhibitory and consisted of membrane hyperpolarization, decreased input resistance, and suppression of excitability. 3. The action of galanin was on the somatic membrane. There were no effects on spike initiation or propagation velocity in the processes. 4. The reversal potential for the hyperpolarizing action of galanin was near the estimated K+ equilibrium potential and was dependent on the concentration of K+ in the bathing medium. 5. Treatment with tetraethylammonium (TEA) broadened the action-potential and enhanced long-lasting hyperpolarizing after-potentials (AH). Application of galanin or depletion of Ca2+ in the bathing medium offset the effects of TEA on the spike and the AH. Galanin or reduced Ca2+ had the same effect when both TEA and tetrodotoxin (TTX) were present. 6. Simultaneous application of TEA and 4-aminopyridine (4-AP) evoked spontaneous spike discharge with broadened spikes and enhanced AH. This activity was suppressed by galanin. 7. Intrasomatic injection of Cs+ in the presence of TTX appeared to abolish all K+ conductances leaving pure Ca2+ spikes in response to depolarizing current pulse. Galanin abolished these Ca2+ spikes. 8. The results suggest two major mechanisms of action for galanin. One is to open K+ channels, decrease input resistance, and hyperpolarize the membrane toward EK+. The second is blockade of voltage gated Ca2+ channels and suppression of the AH by indirect prevention of opening of Ca2+-dependent K+ channels.
Tamura
K
K
Department of Physiology, College of Medicine, Ohio State University, Columbus 43210.
Palmer
J M
JM
Winkelmann
C K
CK
Wood
J D
JD
D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D004594:Electrophysiology; D019004:Galanin; D006168:Guinea Pigs; D008564:Membrane Potentials / Q000187:drug effects; D009197:Myenteric Plexus / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010455:Peptides / Q000494:pharmacology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D000631:Aminopyridines; D010455:Peptides; D013757:Tetraethylammonium Compounds; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D019004:Galanin; D015761:4-Aminopyridine