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Responses of the smooth muscle membrane of the rabbit bladder to intramuscular nerve stimulation were investigated by the micro-electrode and double sucrose-gap methods. The cell generated regular spontaneous action potentials. Acetylcholine produced a maintained increase in the frequency and ATP a transient increase. Noradrenaline only increased the frequency at very high concentrations. Application of short current pulses (50 microseconds) produced an initial excitatory junction potential (e.j.p.) with a superimposed spike, followed by a late depolarization. On some occasions, hyperpolarization of the membrane appeared between initial e.j.p. and the late depolarization. All these responses were abolished by tetrodotoxin. The late depolarization was enhanced by pre-treatment with neostigmine and abolished by atropine. This means that the delayed depolarization is due to activation of the muscarinic receptor. When the late depolarization was abolished, the amplitude of hyperpolarization was enhanced. The e.j.p. and contraction were unaffected by guanethidine, phentolamine, methysergide, mepyramine, quinidine or theophylline. This means that the e.j.p. is not mediated by activation of adrenergic, tryptaminergic, histaminergic or purinergic receptors. ATP reduced the amplitude of the e.j.p. due to depolarization of the membrane and reduction in the membrane resistance. The amplitude of the e.j.p. was gradually reduced by repetitive stimulation (0.5-2.0 Hz). However, the rate of depression was unchanged in the presence of ATP. Dipyridamole did not change the electrical and mechanical responses to field stimulation. These results do not support the proposal that ATP is the non-cholinergic excitatory transmitter. Apamine and tetraethylammonium (TEA) suppressed the hyperpolarization produced by field stimulation but guanethidine did not inhibit the hyperpolarization. Therefore, the hyperpolarization is due to increased K conductance of the membrane but it is not possible to conclude whether this component is due to the inhibitory action of a neurotransmitter or solely to after hyperpolarization of the spike. It was concluded that the rabbit bladder receives both cholinergic and noncholinergic excitatory neurones.
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