On the latency and form of the membrane responses of smooth muscle to the iontophoretic application of acetylcholine or carbachol

Abstract

Acetylcholine or carbachol were applied iontophoretically to longitudinal smooth muscle from tenia or ileum of guinea pigs by a micropipette, while the membrane potential was recorded intracellularly by microelectrode. Contraction of the muscle was prevented by hyperpolarizing the membrane with inward current in a double-sucrose gap apparatus or, occasionally, by the use of a bathing solution made hypertonic by the addition of sucrose. When the tip of the pipette was close to, but not touching the muscle, the depolarization produced had a slow onset. Responses with a more rapid onset could be obtained when the pipette tip was touching or embedded in the muscle strip. The latency was always 100 ms or more, similar to the latency of responses to parasympathetic nerve stimulation. Experiments were done in an attempt to discover if the latency and form of the responses could be fitted by the equation for diffusion of a substance from a point source. The Q10 of the time to peak was 1.6-1.9 compared to the theoretically expected value of 1.3. Decreasing the amount of drug released or increasing the distance of the pipette from the receptors, increased the latency and time to peak of the responses but decreased their size and the duration of their rising phase. These features of the responses were not reproduced by the equation for diffusion from a point source, which predicted responses of shorter latency and greater duration than those observed. The cell membranes of smooth muscle may not be equally sensitive to acetylcholine or carbachol and the more sensitive regions may be less accessible to iontophoretically applied drug. The similarity of the latencies to nerve-released and directly-applied acetylcholine suggests that there is some microscopic property of the receptor or its immediate environment which delays the onset of the effect of the transmitter.