Nifedipine blocks apamin-induced bursting activity in nigral dopamine-containing neurons.
Intrinsic sinusoidal oscillations in membrane potential, characteristic of nigral dopamine cells, are converted to plateau potentials following application of apamin, a potent antagonist of SK-type Ca2+-activated K+ channels. Blockade of these channels also changes neuronal firing pattern from a single-spike pacemaker discharge to a multiple spike bursting pattern. Nifedipine, a selective antagonist of L-type Ca2+ channels, blocks plateau potential generation; however, its effects on firing pattern have yet to be determined. In the present study, extracellular single unit recording techniques were used in conjunction with a brain slice preparation to determine whether nifedipine, in a concentration known to block plateau potential generation, also affects bursting activity. Nifedipine (30 microM) was equipotent in inhibiting the firing rate of control (51.2+/-10.8%) and apamin-treated (44.9+/-5.4%) neurons. Slow firing neurons (<2 Hz) were particularly sensitive to the inhibitory effects of the drug. Apamin-induced bursting was completely suppressed by nifedipine and accompanied by a significant increase in the regularity of firing. By contrast, pacemaker-like activity exhibited by control neurons was unaffected by the drug. These data demonstrate that the intrinsic plateau properties exhibited by DA neurons are responsible for the generation of phasic activity induced following blockade of apamin-sensitive Ca2+-activated K+ channels and provide further support for the involvement of an L-type Ca2+ conductance in mediating this type of activity.
Shepard
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Maryland Psychiatric Research Center, P.O. Box 21247, Catonsville, MD 21228, USA.pshepard@umaryland.edu
Stump
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D000818:Animals; D001030:Apamin / Q000037:antagonists & inhibitors*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004298:Dopamine / Q000032:analysis*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000737:chemistry / Q000187:drug effects*; D009543:Nifedipine / Q000494:pharmacology*; D009991:Oscillometry; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects*
D002121:Calcium Channel Blockers; D001030:Apamin; D009543:Nifedipine; D004298:Dopamine