Kinetic analysis of atropine‐induced alterations in bullfrog ganglionic fast synaptic currents.

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Abstract
The concentration‐ and voltage‐dependent effects of atropine on the fast excitatory post‐synaptic current (e.p.s.c.) of bullfrog sympathetic ganglion cells have been analysed and fitted to a kinetic scheme of open‐channel blockade. Atropine (1‐75 microM) reduced the peak e.p.s.c. amplitude without altering the quantal content or the reversal potential. The e.p.s.c. decay was complex in the presence of atropine, being well fitted by two exponential components. With increasing concentrations of atropine the time constant of the fast component, tau 2, decreased and the time constant of the slow component, tau 1, increased. Over the voltage range ‐30 to ‐100 mV tau 2 exhibited little or no voltage dependence and tau 1 increased with hyperpolarization. The amount of charge moved during the e.p.s.c. was reduced as a function of atropine concentration. Driving functions, which represented the rate of channel opening, were derived from e.p.s.c.s both from control and atropine‐treated cells. The characteristics of the driving functions did not vary with membrane voltage, but the driving functions were shorter in duration from atropine‐treated than control cells. The area under the driving function decreased as a function of atropine concentration. The decay time constants and the amplitude ratio of the exponential components were used to calculate the closing, blocking, and unblocking rate constants, alpha, G, and F. alpha and F remained constant with increasing atropine concentration, but G declined significantly. The voltage dependence of the equilibrium constant, G/F, implied that the transient blocking site for atropine is halfway through the ionic channel. The sequential model does not predict the concentration‐dependent decrease in the blocking rate, G, or in the charge moved during an e.p.s.c. We conclude that atropine has an action more complex than simple channel blockade in sympathetic ganglion cells.