Lobeline inhibits Ca2+ current in cultured neurones from rat sympathetic ganglia.
The effect of lobeline was studied on the voltage-activated Ca2+ current in sympathetic neurones from the rat superior cervical ganglia using the whole-cell variant of the patch-clamp technique. Lobeline (10-300 microM) inhibited the Ca2+ current evoked by voltage steps from -80 mV (holding potential) to 0 mV (test potential) in a dose dependent manner. The inhibitory effects of noradrenaline (10 microM) and lobeline (100 microM) were compared using a prepulse protocol with high (+80 mV) depolarization. Within the same cell depolarizing prepulses decreased the inhibitory effect of noradrenaline but did not change the extent of lobeline inhibition. Addition of GTPgammaS (300 microM) to the pipette solution did not prevent the inhibitory effect of lobeline (100 microM) but greatly reduced that of noradrenaline (100 microM). Our experiments suggest, that the weak nicotinic agonist lobeline exerts a direct blocking effect on Ca2+ channels at concentrations commonly used to release transmitters.
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Department of Pharmacology, Institute of Experimental Medicine, Hungarian Academy of Sciences, Hungary. ptt5@midway.uchicago.edu
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D000818:Animals; D000831:Animals, Newborn; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005071:Evoked Potentials; D005728:Ganglia, Sympathetic / Q000187:drug effects*; D008120:Lobeline / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000187:drug effects*
D002121:Calcium Channel Blockers; D008120:Lobeline; D009638:Norepinephrine