Synaptic delay in the heart: an ionophoretic study.

Abstract

SUMMARY1. Neurotransmitters were applied ionophoretically to spontaneously beating clusters of ventricular muscle cells cultured from neonatal rats.2. Acetylcholine or its analogue carbachol produced hyperpolarization and decreased the rate of spontaneous beating. These responses had minimum latencies of about 250 msec and total durations of 6-12 sec.3. Noradrenaline, adrenaline or isoprenaline increased the rate of spontaneous beating. The minimum latency for this effect was 3-6 sec. Following a single brief pulse the rate remained elevated for 2 min or more.4. Chronotropic responses of intact atria from adult rats to stimulation of the autonomic nerves were of similar time course to responses of the cultured muscle cells.5. Calculations based on the theory of diffusion showed that access of drugs to their receptors could not be rate-limiting for the observed responses, unless a diffusion barrier of rather special properties was postulated. A number of other explanations for the long latencies have been ruled out; these are most likely to be due to some physical or chemical process occurring in or under the cell membrane.6. Attempts to mimic responses to catecholamines by intracellular application of cyclic AMP were unsuccessful, perhaps because the release of nucleotide from the pipettes was insufficient. A theoretical treatment suggests that ionophoretic efflux of anions might be greatly diminished by the opposing electro-osmotic flux.

Changes by acetylcholine of membrane currents in rabbit cardiac Purkinje fibres.

“…The maximum current change was reached about 5 s after the beginning of ACh application. Latency period as well as time to peak were very long compared to values described for the electrophysiological changes following ACh application by ionophoresis in other cardiac preparations (Hill-Smith & Purves, 1978;Osterrieder, Yang & Trautwein, 1981). In ourexperiments, little attention was paid to minimize the distance between the ACh-filled electrode and the fibre, so that diffusion of ACh from the electrode to and along the fibre may account for a great part of the long delays for ACh action.…”

Cholinergic and catecholaminergic receptors in the Xenopus oocyte membrane

“…Although it is still not entirely clear if these responses are caused by a direct drug action on the membrane of the oocytes, similarly long delays (3-15 sec) have been observed following catecholamine application to heart cells (Niedergerke & Page, 1977;Hill-Smith & Purves, 1978).…”

“…Miledi, unpublished). In contrast, the delay is several orders of magnitude longer in muscarinic receptors in various nerve and muscle cells, where the responses to ionophoretically applied ACh start with a delay varying from 150 msec to 30 sec (Krnjevic & Phillis, 1963;Bolton, 1976;Hartzell, Kuffler, Stickgold & Yoshikami, 1977;Hill-Smith & Purves, 1978).…”

Baroreflex sensitivity, blood pressure buffering, and resonance: what are the links? Computer simulation of healthy subjects and heart failure patients

“…It appears that BRS (the TF between 0.05 and 0.15 Hz) may lower with high sympathetic gain to the heart. This is caused by the differences in the latencies/time constants in the sympathetic (17,41) and vagal (6,48) limbs, bringing the vagal and the sympathetic effects in counterphase in the BRS frequency band. Hence, there are situations thinkable in which cancellation of vagal effects on heart rate by concurring sympathetic effects on heart rate in counterphase incorrectly suggest a deficient baroreflex.…”

“…Hence, there are situations thinkable in which cancellation of vagal effects on heart rate by concurring sympathetic effects on heart rate in counterphase incorrectly suggest a deficient baroreflex. For higher frequencies, the influence of the sympathetic feedback gain weakens and disappears because of a low pass filtering effect caused by slow neurotransmitter diffusion at the synaptic clefts (17).…”