Reduction of the N-type calcium current by noradrenaline in neurones of rabbit vesical parasympathetic ganglia.

1. Intracellular and single-electrode voltage-clamp recordings were made from neurones of vesical parasympathetic ganglia (VPG) isolated from the rabbit urinary bladder. 2. Noradrenaline (NA, 0.5-5 microM) shortened the duration of the action potentials and depressed the amplitudes of both spike after-hyperpolarization and after-current. 3. Voltage-dependent calcium currents (ICa) were recorded by using microelectrodes filled with 2 M-caesium chloride in a superfusing solution containing tetraethylammonium (TEA, 50 mM) and tetrodotoxin (TTX, 500 nM). Noradrenaline (0.5-5 microM) depressed both the ICa and the tail current evoked by depolarizing voltage jumps from -100 to -50 mV to -30 to +20 mV. 4. Substitution of barium for calcium also produced an inward current (IBa) with no obvious tail current. Noradrenaline (1 microM) reduced the magnitude of the IBa without affecting the voltage dependence of the current-voltage relationship for IBa. 5. Yohimbine (1 microM), but not prazosin (1 microM) or propranolol (1 microM), antagonized the NA-induced inhibition of the IBa. UK 14304, a potent alpha 2-adrenoceptor agonist, mimicked NA in depressing the IBa. 6. The transient low-threshold (T), the transient high-threshold (N) and the slowly inactivating high-threshold (L) calcium currents co-existed in VPG neurones. 7. Noradrenaline reduced the IBa evoked at clamp potentials more positive than -20 mV from holding potentials near the resting membrane potential (-70 to -50 mV). Under these conditions, the IBa consisted primarily of N- and L-current components. In contrast, NA had no effect on the isolated T- and L-currents. It is concluded that NA selectively inhibits the N-type calcium channels by an action at alpha 2-adrenoceptors in the rabbit VPG neurones.