Physiological role of desensitized cholinoceptors in skeletal muscle

Abstract

The effect of desensitized cholinoceptors on the time course of end-plate currents was evaluated in frog skeletal muscle at a high (physiological) level of acetylcholine secretion in the presence of active acetylcholinesterase, with two-electrode recording of the membrane potential. When the number of cholinoceptors was small so that they did not appreciably affect the amplitude of end-plate currents or the parameters of onequantum responses (miniature currents), the decay of multiquantum currents was significantly accelerated. Moreover, the presence of cholinoceptors drastically reduced the ability of acetylcholinesterase inhibitors to prolong the decay of end-plate currents. It is suggested that desensitized cholinoceptors in a synapse with a physiological level of acetylcholine secretion and active acetylcholinesterase may bind free acetylcholine with high affinity and thus supplement the well-known physiological role of acetylcholinesterase in limiting the reactivation of postsynaptic membrane cholinoceptors. Key Words: synapse; acetylcholine; desensitizationDesensitization of a muscle cell membrane, i.e., its reduced sensitivity to the neurotransmitter acetylcholine (ACh), may be induced by exogenous cholinomimetics, including depolarizing myorelaxants [10], and by the endogenous ACh released from nerve endings [5,6,12]. How desensitization affects the parameters of synaptic signals and what the functional role of this phenomenon is in skeletal muscle have not been ascertained. Desensitization, if strong, appears to be manifested in lowered amplitudes of synaptie signals as a result of a decrease in the number of receptors capable of opening ion channels when ACh is active. It has also been suggested that desensitized receptors may play a functional role in the redistribution of free ACh in the synaptic cleft through high-affinity binding of the transmitter [13]. Evidence in support of this hypothesis has so far been obtained only for muscles with inhibited acetylcholinesterase and low levels of ACh secretion. In view of this, we tried in this study to elucidate the functional role of desensitized receptors in the presence of active acetylcholinesterase and a high (physiological) level of ACh secretion, i.e., under conditions that, like acetylcholinestemse inhibition, increase the local concentration of this transmitter in the synaptic cleft as compared to its level in the case of one-quantum responses. MATERIALS AND METHODSThe experiment was conducted on neuromuscular preparations of the sciatic nerve-sartorius muscle from Rana ridibunda frogs, with two-electrode recording of the membrane potential. The muscle was continuously peffused with physiological solution of the following composition (mmol/liter): NaC1 113, KC1 2.5, CaC12 1.8, NaHCO 3 2.4; pH 7.2-7.4. To maintain the induced ACh secretion at a high level close to the physiological one, muscle contractions were prevented by transecting the muscle [1]. The nerve was stimulated at a fre-

Bradykinin effect on conduction of rhythmic series of pulses through the neuromuscular synapse

“…The time course of secretion during a single synaptic transfer was evaluated by the deconvolution method [8,14]. The methods were described in detail previously [1][2][3]. …”