Drugs may modify transmission by affecting either the release of transmitter or the interaction of ACh with its receptor. An increase in transmitter release is produced by substances that induce repetitive firing in the motor nerve, prolong the nerve action potential, or promote Ca++ influx at the nerve terminal. An increase in the postjunctional response is produced by drugs that inhibit AChE (and thereby increase the synaptic concentration of ACh), whereas a decrease in response is produced by drugs that block the binding sites or ion-conducting channel of the AChR.
Changes in miniature EPC frequency, amplitude, and duration can be used to identify the sites of drug action. In general, a change in frequency indicates a prejunctional action, while a change in amplitude reflects a postjunctional effect. Drugs that inhibit AChE give rise to a larger and more prolonged miniature EPC, whereas those that block the AChR binding site produce a decrease in miniature EPC amplitude. Agents that obstruct the open channel of the AChR cause a reduction in miniature EPC amplitude and duration.
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