Augmentation of bursting pacemaker activity by serotonin in an identified Achatina fulica neurone: an increase in sodium- and calcium-activated negative slope resistance via cyclic-AMP-dependent protein phosphorylation.
The mechanism of serotonin (5-HT) action on bursting activity was examined in a bursting pacemaker neurone of the snail Achatina fulica. 5-HT augmented both the depolarizing and post-burst-hyperpolarizing phases of the bursting cycle in a dose-dependent manner. This biogenic amine also enhanced the negative slope resistance (NSR), which was normally detectable at membrane potentials between -40 and -20 mV, and produced another NSR at voltages between -20 and 0 mV. The former NSR disappeared in Na(+)-free saline and the latter was abolished by replacement with Co(2+)-substituted Ca(2+)-free saline. Both isobutylmethylxanthine, extracellular applied, and intracellularly applied cyclic AMP simulated a 5-HT effect on the current-voltage relationships. In contrast, the 5-HT effect was suppressed in a dose-dependent manner by prior treatment with a cyclic-AMP-dependent protein kinase inhibitor, isoquinoline sulphonamide. Similar suppression was observed after intracellular injection of a cyclic-AMP-dependent protein kinase inhibitor isolated from bovine muscle. These results suggest that 5-HT may augment the bursting pacemaker activity by its stimulatory effect on both the slow Na+ channels and the Ca2+ channels through cyclic-AMP-dependent protein phosphorylation.
Funase
K
K
School of Allied Medical Sciences, Nagasaki University, Japan.
Watanabe
K
K
Onozuka
M
M
D000200:Action Potentials; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D005724:Ganglia / Q000166:cytology / Q000378:metabolism; D066298:In Vitro Techniques; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D012701:Serotonin / Q000502:physiology*; D012908:Snails; D012964:Sodium / Q000378:metabolism; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D047428:Protein Kinase Inhibitors; D013757:Tetraethylammonium Compounds; D012701:Serotonin; D019789:Tetraethylammonium; D012964:Sodium; D000242:Cyclic AMP; D002118:Calcium