Clindamycin-induced alteration of ganglionic function. II. Effect of nicotinic receptor-channel function.
The postsynaptic effects of clindamycin have been analyzed in bullfrog sympathetic ganglion B cells using single electrode current and voltage clamp recordings and two electrode voltage clamp measurements. Clindamycin added to the bathing solution in the concentration range, 2.5 x 10(-4) to 5 x 10(-4) M, inhibited fast ganglionic transmission. In addition, local application of clindamycin decreased depolarizations produced by direct application of acetylcholine and decreased the amplitude of miniature excitatory postsynaptic potentials (MEPSPs) evoked by tetanic stimulation of the preganglionic trunk. In contrast, clindamycin did not change the amplitude or time course of the slow EPSP elicited by preganglionic stimulation (30 Hz for 10 s) or muscarinic depolarizations produced by local acetylcholine application to preparations pretreated with 25-50 microM (+)-tubocurarine. In voltage-clamped ganglion cells, excitatory postsynaptic current (EPSC) amplitude initially was increased and then decreased with increasing concentrations of clindamycin (0.5 x 10(-5) to 2.5 x 10(-4) M). The EPSC time course in control cells was exponential. After exposure to clindamycin, the EPSC decay was composed of two exponential components. The time constant of the fast component decreased and the time constant of the slow component increased with increasing concentrations of clindamycin. The two time constants of EPSCs obtained in clindamycin were independent of membrane voltage between -50 and -100 mV. We concluded that the block of fast ganglionic transmission is primarily due to a postsynaptic site of action, at least part of which is due to a concentration-dependent, but voltage-independent blockade of open nicotinic receptor channel complexes.
Konopka
L M
LM
Department of Anatomy and Neurobiology, College of Medicine, University of Vermont, Burlington 05405.
Neel
D S
DS
Parsons
R L
RL
D000109:Acetylcholine / Q000494:pharmacology*; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002981:Clindamycin / Q000494:pharmacology*; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D011892:Rana catesbeiana; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*; D012016:Reference Values; D009435:Synaptic Transmission / Q000187:drug effects*; D014403:Tubocurarine / Q000494:pharmacology
D007473:Ion Channels; D011978:Receptors, Nicotinic; D002981:Clindamycin; D000109:Acetylcholine; D014403:Tubocurarine