Aguayo_1986_J.Pharmacol.Exp.Ther_239_25

The effects of the thienyl analog of phencyclidine, 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP), were examined on the end-plate region of the frog neuromuscular junction using a two microelectrode voltage clamp technique. Among the phencyclidine analogs studied, TCP was the most potent in blocking the end-plate current (EPC), producing the largest voltage- and time-dependent blockade. The current-voltage relationship in the presence of TCP (5-25 microM) displayed a large hysteresis loop and a negative slope conductance at hyperpolarized membrane potentials. The rate of decay of the EPC increased linearly with drug concentration, but the voltage-sensitivity of this parameter remained essentially unchanged. The reduction of the peak amplitude, in contrast to the alterations in the kinetics of EPC decay, were influenced by temperature and length of the conditioning pulse. The hysteresis loop in the EPC amplitudes was eliminated at low temperatures (10 degrees C) and when short conditioning voltage pulses (less than 100 msec) were used. At negative membrane potentials, trains of EPCs evoked at a rate of 0.33 Hz decreased progressively in amplitude, the relationship between peak and amplitude and time being approximately exponential. The rate of blockade was voltage-dependent, increasing by about 1.7-fold with a 70-mV membrane hyperpolarization. However, at positive membrane potentials, the peak amplitude of the EPC recovered linearly with time such that by the 150th pulse it was about 4 times the first EPC, a value similar to that obtained under control conditions.(ABSTRACT TRUNCATED AT 250 WORDS)