Vasoactive intestinal polypeptide depolarizations in cat bladder parasympathetic ganglia.

The effect of vasoactive intestinal polypeptide (VIP) on the neuronal membranes of isolated cat vesical pelvic ganglia and its underlying ionic mechanism were examined by means of intracellular recording and voltage-clamp techniques. Application of VIP (0.05-50 microM) to the neurones by pressure 'puff' ejection through a micropipette placed close to the neurones produced a depolarizing response (2-15 mV) in 83% of neurones tested; this effect was concentration dependent. The VIP-induced depolarization frequently evoked spontaneous action potentials in quiescent neurones and increased the frequency of action potentials in spontaneously firing neurones. The VIP depolarization was not blocked in a Ca2+-free, high-Mg2+ solution or in a solution containing hexamethonium (1 mM) and atropine (1 microM). Tetrodotoxin (TTX; 1 microM) also did not affect the VIP depolarization. The VIP depolarization was associated with an increase in membrane resistance and the slope of a current-voltage relation (I-V curve) was increased by VIP. Conditioning hyperpolarization and depolarization of the membrane increased and decreased the amplitude of the VIP depolarization, respectively. The VIP depolarization reversed polarity around--100 mV. The reversal potential shifted about 20 mV to a more positive level in a high-K+ (10 mM) solution in accord with the Nernst equation. Substituting Cl- with isethionate in the superfusate did not affect the reversal potential of the VIP depolarization. Closure of M-channels does not underlie VIP action since the VIP depolarization was enhanced by muscarine (10 microM) and unchanged in the presence of Ba (5 mM), or intracellular or extracellular Cs+, conditions known to block the M-channels (Adams, Brown & Constanti, 1982a, b). Tetraethylammonium (TEA; 20 mM) also did not affect the VIP depolarization. Voltage-clamp analyses showed that VIP applied by pressure ejection produced an inward current of 80-110 pA associated with a decrease in membrane conductance (from 2.8 to 3.5 nS) at a holding potential of--60 mV. VIP inward current was diminished by either repetitive or continuous application of VIP (5 microM) suggesting desensitization of the VIP receptor. It is concluded that VIP produces a depolarization in neurones of bladder parasympathetic ganglia by decreasing a K+ conductance, the pharmacological characteristics of which are unlike previously described K+ conductance mechanisms.