Effects of nerve stimulation on spontaneously active preparations of the guinea pig ureter

The effects of intrinsic nerve stimulation on the spontaneous electrical activity of the smooth muscle cells of the guinea pig ureter still attached to its renal pelvis were investigated using standard intracellular microelectrode techniques. Action potentials discharged spontaneously at a frequency of 3.3 +/- 0.2 min(-1) (n = 67) and consisted of an initial rapidly rising spike, followed by a variable period (0.2-5 s) of membrane potential oscillation and a quiescent plateau phase which was terminated by an abrupt repolarisation and after-hyperpolarisation to -66 mV. Transmural electrical stimulation (20-50 Hz for 2 s) transiently decreased the frequency of action potential discharge; the half-amplitude duration of the following action potentials, however, was transiently increased to 156 +/- 12% of control. Substance P (1 microM applied for 2 min) or neurokinin A (100 nM for 2 min) transiently increased the frequency of action potential discharge to 155 +/- 19% and 142 +/- 21%, respectively, of control. The excitatory actions of nerve stimulation or agonist application were reduced by the tachykinin antagonist, MEN 10,627 (1-3 microM), while the inhibitory actions of nerve stimulation were enhanced by MEN 10,627 (1 microM) or thiorphan (1 microM). Capsaicin (10 microM for 10-15 min) also evoked a transient increase in the frequency and half-amplitude duration of the ureteric action potentials, in a manner blocked by MEN 10,627 (3 microM), which was followed by a long period of membrane potential quiescence. Human calcitonin gene related peptide (hCGRP) (100 nM applied for 2-5 min) induced a time-dependent decrease in the frequency amplitude and duration of the spontaneous action potentials, in a manner blocked by glibenclamide (1 microM). It was concluded that the nerve-evoked excitatory and inhibitory changes in the parameters of the spontaneous ureteric action potentials arise from the release of the sensory neuropeptides, tachykinins and CGRP, respectively.