Nicotine is no longer possible, even in the face of an intensive and synchronized release of ACh (C). Although nicotine mimics the action of ACh at the receptors, it cannot duplicate the time course of intrasynaptic agonist concentration required for appropriate high-frequency ganglionic activation. The concentration of nicotine in the synaptic cleft can neither build up as rapidly as that of ACh released from nerve terminals nor can nicotine be eliminated from the synaptic cleft as quickly as ACh. The ganglionic effects of ACh can be blocked by tetraethylammonium, hexamethonium, and other substances (ganglionic blockers). None of these has intrinsic. | 108 Nicotine Ganglionic Transmission Whether sympathetic or parasympathetic all efferent visceromotor nerves are made up of two serially connected neurons. The point of contact synapse between the first and second neurons occurs mainly in ganglia therefore the first neuron is referred to as preganglionic and efferents of the second as postganglionic. Electrical excitation action potential of the first neuron causes the release of acetylcholine ACh within the ganglia. ACh stimulates receptors located on the subsynaptic membrane of the second neuron. Activation of these receptors causes the nonspecific cation channel to open. The resulting influx of Na leads to a membrane depolarization. If a sufficient number of receptors is activated simultaneously a threshold potential is reached at which the membrane undergoes rapid depolarization in the form of a propagated action potential. Normally not all preganglionic impulses elicit a propagated response in the second neuron. The ganglionic synapse acts like a frequency filter A . The effect of ACh elicited at receptors on the ganglionic neuronal membrane can be imitated by nicotine . it involves nicotinic cholinoceptors. Ganglionic action of nicotine. If a small dose of nicotine is given the ganglionic cholinoceptors are activated. The membrane depolarizes partially but fails to reach the firing threshold. However at this point an amount of released ACh smaller than that normally required will be sufficient to elicit a propagated action potential. At a low concentration nicotine acts as a ganglionic stimulant it alters the filter function of the ganglionic synapse allowing action potential frequency in the second neuron to approach that of the first B . At higher concentrations nicotine acts to block ganglionic transmission. Simultaneous activation of many nicotinic cholinoceptors depolarizes the ganglionic cell membrane to such an extent that generation of action potentials is no longer possible even in the face of an
