Cocaine elicits action potential bursts in a central snail neuron: the role of delayed rectifying K(+) current
by
Chen YH, Lin CH, Lin PL, Tsai MC.
Department of Nursing,
Yuan-Pei University of Science and Technology,
No.306, Yuan-Pei Road, Hsinchu, Taiwan.
Neuroscience. 2005 Dec 22;
ABSTRACTThe effects of cocaine were studied in an identifiable RP4 neuron of the African snail, Achatina fulica Ferussac, using the two-electrode voltage-clamp method. The RP4 neuron generated spontaneous action potentials and bath application of cocaine (0.3 approximately 1mM) reversibly elicited action potential bursts of the central RP4 neuron in a concentration-dependent manner. The action potential bursts were not blocked when neurons were immersed in high-Mg(2+)solution, Ca(2+)-free solution, nor after continuous perfusion with atropine, d-tubocurarine, propranolol, prazosin, haloperidol, or sulpiride. Similarly, the action potential bursts were not abolished by pretreatment with N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride, (9S,10S,12R)-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid hexyl ester or anisomycin. Injection of hyperpolarizing current at an intensity of greater than 2 nA effectively suppressed the cocaine-elicited action potential bursts and no postsynaptic potentials were observed under these conditions. These results suggest that the generation of action potential bursts elicited by cocaine was not due to (1) the synaptic effects of neurotransmitters, (2) the cholinergic, adrenergic or dopaminergic receptors of the excitable membrane, or (3) the cAMP second messengers and new protein synthesis of the RP4 neuron. Notably, the induction of action potential bursts was blocked by pretreatment with 1-[6-[((17beta)-3-methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dione. Voltage-clamp studies conducted on the RP4 neuron revealed that cocaine at 0.3mM decreased (1) the Ca(2+) current, (2) the delayed rectifying K(+) current, (3) the fast-inactivating K(+) current and (4) the Ca(2+)-activated K(+) current, but had no remarkable effects on the Na(+) current. Perfusion with Ca(2+)-free solution, which may abolish the Ca(2+) current and Ca(2+)-activated K(+) current, did not cause any bursts of action potentials in control RP4 neurons. Application of 4-aminopyridine, an inhibitor of fast-inactivating K(+) current, and paxilline, an inhibitor of Ca(2+)-activated K(+) current, failed to elicit action potential bursts, whereas tetraethylammonium chloride, a blocker of Ca(2+)-activated K(+) current and delayed rectifying K(+) current, and tacrine, an inhibitor of delayed rectifying K(+) current, successfully elicited action potential bursts. Further, while 1-[6-[((17beta)-3-methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dione did not affect the delayed rectifying K(+) current of the RP4 neuron, 1-[6-[((17beta)-3-methoxyestra-1,3,5[10]-trien-17-yl)amino]hexyl]-1H-pyrrole-2,5-dione decreased the inhibitory effect of cocaine on the delayed rectifying K(+) current. It is concluded that cocaine elicits action potential bursts in the central snail RP4 neuron and that the effect is closely related to the inhibitory effects on the delayed rectifying K(+) current.Incas
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