1. Arterioles were impaled with two independent micro-electrodes, one to pass current and the other to record membrane potential. 2. When current was injected into one branch of an arteriole, a membrane potential change could be detected either in the same branch or in an adjoining branch indicating that the arteriolar smooth muscle cells were electrically connected. 3. Fine dissection of the arteriolar tree gave short segments of arteriole which appeared to behave electrically as short cables with sealed ends. 4. Analysis of the electrotonic potentials recorded from isolated segments of arterioles allowed a determination of the arteriole cable properties. 5. Using the data from the cable analyses it was concluded that the junctional current underlying an excitatory junction potential has a duration that is brief when compared with that of the potential.

Stimulation of the endothelial lining of arteries with acetylcholine results in the release of a diffusible substance that relaxes and hyperpolarizes the underlying smooth muscle. Nitric oxide (NO) has been a candidate for this substance, termed endothelium-derived relaxing factor. But there are several observations that argue against the involvement of NO in acetylcholine-induced hyperpolarization. First, exogenous NO has no effect on the membrane potential of canine mesenteric arteries. Second, although haemoglobin (believed to bind and inactivate NO (refs 11-15)) and methylene blue (which prevents the stimulation of guanylate cyclase) inhibit relaxation, neither has an effect on hyperpolarization. Finally, nitroprusside, thought to generate NO in vascular smooth muscle, relaxes rat aorta without increasing rubidium efflux. Nevertheless, nitrovasodilators, nitroprusside and nitroglycerin cause hyperpolarization in some arteries. NO might therefore be responsible for at least part of the hyperpolarization induced by acetylcholine. We now report that hyperpolarization and relaxation evoked by acetylcholine are reduced by NG-monomethyl-L-arginine, an inhibitor of NO biosynthesis from L-arginine. Thus NO derived from the endothelium can cause hyperpolarization of vascular smooth muscle, which might also contribute to relaxation by closing voltage-dependent calcium channels. Our findings raise the possibility that hyperpolarization might be a component of NO signal transduction in neurons or inflammatory cells.

SUMMARY1. The excitatory effects of acetylcholine (ACh) on an identified group of Aplysia neurones have been studied under voltage clamp in an attempt to measure the average life time, r, of the channels opened by ACh and the elementary current, iel, flowing through these channels. 7. Inward ACh induced currents can still be observed in solutions where all Na has been replaced by Cs, Mg, or Ca.8. iel increases when Na is replaced by Cs; it decreases when Na is replaced by Mg or Ca. In all Na-free solutions, T is larger than in Na sea water: the lengthening of r is largest for Ca sea water, smallest for Cs sea water. An interpretation of these changes P. ASCHER, A. MARTY AND T. 0. NEILD of T is proposed. This interpretation may also account for the voltage sensitivity of T in normal sea water.9. Partial replacement of NaCl by TrisCl strikingly reduces the ACh induced current. T is not modified by Tris substitution, and the reduction of the total current is entirely accounted for by a steep decrease of tel. Tris does not seem to affect the pore opening and closing processes, but to block the ACh controlled channel.

The conduction of vasodilation along resistance vessels has been presumed to reflect the electrotonic spread of hyperpolarization from cell to cell along the vessel wall through gap junction channels. However, the vasomotor response to acetylcholine (ACh) encompasses greater distances than can be explained by passive decay. To investigate the underlying mechanism for this behavior, we tested the hypothesis that ACh augments the conduction of hyperpolarization. Feed arteries (n = 23; diameter, 58 +/- 4 microm; segment length, 2-8 mm) were isolated from the hamster retractor muscle, cannulated at each end, and pressurized to 75 mmHg (at 37 degrees C). Vessels were impaled with one or two dye-containing microelectrodes simultaneously (separation distance, 50 microm to 3.5 mm). Membrane potential (E(m)) (rest, approximately -30 mV) and electrical responses were similar between endothelium and smooth muscle, as predicted for robust myoendothelial coupling. Current injection (-0.8 nA, 1.5 s) evoked hyperpolarization (-10 +/- 1 mV; membrane time constant, 240 ms) that conducted along the vessel with a length constant (lambda) = 1.2 +/- 0.1 mm; spontaneous E(m) oscillations (approximately 1 Hz) decayed with lambda = 1.2 + 0.1 mm. In contrast, ACh microiontophoresis (500 nA, 500 ms, 1 microm tip) evoked hyperpolarization (-14 +/- 2 mV) that conducted with lambda = 1.9 +/- 0.1 mm, 60% further (P < 0.05) than responses evoked by purely electrical stimuli. These findings indicate that ACh augments the conduction of hyperpolarization along the vessel wall.

We have recorded the responses of arteriolar smooth muscle cells to iontophoretically applied noradrenaline. Records of both muscle movement and muscle membrane potential were made. We found that two distinct types of response could be detected, depending on the position of the noradrenaline micropipette. One type of response consisted of a localised constriction near the noradrenaline source: this effect could be abolished by the alpha-antagonist phentolamine and was not associated with a change in arteriolar membrane potential. The other type of response was a depolarisation similar to the excitatory junction potentials (e.j.ps) produced by sumpathetic nerve stimulation. These observations suggest that there are two populations of receptors for noradrenaline on arterioles, and could explain the paradoxical failure of alpha-antagonists to block neuromuscular transmission at some sutonomic end organs such as the vas deferens, arteries and arterioles.