A slow voltage-dependent Na(+)-current induced by 5-hydroxytryptamine and the G-protein-coupled activation mechanism in the ganglion cells of Aplysia.
Application of 5-hydroxytryptamine (5HT) induces a slowly depolarizing response in the neurons of Aplysia abdominal ganglion. In voltage-clamped cells, 5HT induced a slow inward current that increased steeply with membrane depolarization from -85 mV showing a negative slope conductance, but never reversed into outward when hyperpolarized beyond the equilibrium potential for K+. The 5HT-induced response was markedly augmented in Ca(2+)-free media, but depressed in Na(+)-free media, and unaffected by a change in external potassium. Intracellular injection of guanosine 5'-O-(2-thiodiphosphate) (GDP beta S) significantly depressed the 5HT response in a dose-dependent way. Injection of cholera toxin (CTX) selectively blocked the 5HT-induced response, the effect being irreversible. Neither 3'-deoxyadenosine, an inhibitor of adenylate cyclase, nor H-8, an inhibitor of protein kinase A, depressed the 5HT response. 3-Isobutyl-1-methylxanthine (IBMX) did not augment the 5HT response appreciably. The 5HT responses were not depressed at all during a saturated response to Br-cyclic AMP injected intracellularly. It was concluded that the 5HT response is produced by opening of the voltage-dependent Na(+)-channels with activation of CTX-sensitive G-protein but not necessarily with an increase in intracellular cyclic AMP.
Kudo
A
A
Department of Physiology, School of Medicine, Iwate Medical University, Morioka, Japan.
Sasaki
K
K
Tamazawa
Y
Y
Matsumoto
M
M
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001048:Aplysia; D002772:Cholera Toxin / Q000494:pharmacology; D004563:Electrochemistry; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005724:Ganglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D008564:Membrane Potentials; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D013873:Thionucleotides / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D013873:Thionucleotides; D010566:Virulence Factors, Bordetella; D006153:Guanosine Diphosphate; D015124:8-Bromo Cyclic Adenosine Monophosphate; D012701:Serotonin; C023427:guanosine 5'-O-(2-thiodiphosphate); D002772:Cholera Toxin; D012964:Sodium; D011494:Protein Kinases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D015056:1-Methyl-3-isobutylxanthine