Theoretical analysis of mode of heptanol action on smooth muscle synaptic potentials

A theoretical analysis has been undertaken of the synaptic or “junction” potentials of syncytial smooth muscle in order to examine the most likely mode of action of a chemical, 1-heptanol, that has profound effects on neurotransmission in this tissue. The smooth muscle syncytium of the mammalian vas deferens has been modelled as a bidomain electrical grid which allows simulation of the spontaneous and evoked excitatory junction potentials (sEJPs and eEJPs) observed experimentally in this organ. Two hypotheses of heptanol action raised by its effects on the electrical responses of the vas have been examined: (i) inhibition of cell-to-cell electrical coupling in smooth muscle; (ii) inhibition of the stimulation-evoked release of neurotransmitter from the autonomic nerve supply. We find that the range of experimental findings can be explained consistently on the basis of the second, but not the first, hypothesis. Our results thus cast doubt on the current belief that heptanol, at the concentrations used empirically, specifically uncouples smooth muscle cells from one another, and indicate a novel, previously unsuspected biophysical mode of action which merits close scrutiny