Are Junction Potentials Essential? Dual Mechanism of Smooth Muscle Cell Activation by Transmitter Released From Autonomic Nerves

Abstract

Stimulation of autonomic nerves supplying smooth muscle tissues often evokes either an e.j.p. or an i.j.p. which involves a shift in the membrane potential such that the entry of calcium into the cell through voltage-sensitive calcium channels is likely to be increased or decreased respectively. In smooth muscle which freely discharges action potentials either spontaneously or in response to excitatory influences in vivo, the change in membrane potential will alter the rate of action potential discharge and so the tension developed by the smooth muscle. In this way there is modulation of the rate of entry of calcium, or its release within the cell, by a voltage-dependent mechanism entrained by the junction potential, as the action potential represents the operation of voltage-dependent calcium channels. In smooth muscles not freely discharging action potentials, the numbers of open calcium channels may change with depolarization, or even hyperpolarization, so the junction potential again brings into play a voltage-dependent mechanism of calcium entry. However, a dual mechanism of neurotransmission seems to operate at many autonomic nerve-smooth muscle junctions such that voltage-independent mechanisms coexist with voltage-dependent mechanisms. It is now generally accepted that activation of receptors on smooth muscle cells caused by bathing smooth muscles in solutions containing excitatory transmitters can bring into operation processes which are not voltage-dependent and which do not depend on modulation of the rate of action potential discharge. Up to the present it has been by no means certain that when released from autonomic nerves these excitatory transmitters (ACh, noradrenaline, substance P and n.a.n.c. excitatory transmitters) could also act in the same voltage-independent way - not least because studies of smooth muscle cells at the cellular level have been dominated by membrane potential recording (by micro-electrode) which has revealed the e.j.p. or some form of depolarization as a seemingly ubiquitous feature of excitatory autonomic junctions of nerve and smooth muscle cells. However, experiments show that under conditions when the e.j.p. and/or the action potential are abolished or severely impaired by drug application, substantial nerve-evoked smooth muscle contractions may occur at many autonomic junctions. Conversely, severe impairment of nerve-evoked contraction may occur in some cases with excitatory-receptor antagonists without loss, or even in some cases any impairment, of the e.j.p. which presumably depends on a different receptor type.(ABSTRACT TRUNCATED AT 400 WORDS)

Effect of cromakalim on bronchoconstriction evoked by cholinergic nerve stimulation in guinea‐pig isolated trachea

“…However, non-specific effects of cromakalim on neuronal function cannot be ruled out. It is believed that ACh can bring about contraction in smooth muscle through at least three, possibly independent, mechanisms, namely by promoting Ca2"-influx through both receptor-operated Ca2-channels (ROCs) and voltage-operated Ca 2-channels (VOCs) and by releasing Ca2 + from intracellular storage sites (Bolton & Large, 1986). By enhancing K+-efflux and thus causing hyperpolarisation, cromakalim would be expected to oppose the depolarisation evoked by bronchoconstrictor agents and thereby reduce influx of Ca2+ through VOCs.…”

Electrophysiological Properties of Inhibitory Junction Potential in Murine Lower Oesophageal Sphincter.

“…The inhibitory neural regulation in LOS has been well investigated, and nonadrenergic noncholinergic (NANC) nerves have been reported as playing an important role in causing of relaxation in this region (Hoyle and Burnstock, 1989). Inhibitory junction potential (IJP) evoked by stimulation of enteric autonomic nerves causes not all but a part of the relaxation evoked by stimulation of enteric autonomic nerves (Bolton and Large, 1986;Imaeda et al, 1998). So IJP could be an important phenomenon for investigating the electrophysiological properties of inhibitory neural transmission.…”

Acetylcholine activates non‐selective cation and chloride conductances in canine and guinea‐pig tracheal myocytes.

“…In addition to this lack of understanding of the ionic mechanisms, the physiological relevance of excitatory junction potentials and of membrane depolarization in airway smooth muscle has been questioned (Bolton & Large, 1986;Daniel et al 1991). It might be presumed that depolarization causes opening of voltagedependent Ca2" channels, allowing influx of extracellular Ca2+ (Ca2+), and subsequent activation of the contractile machinery.…”