Abstract
Opiates1,2 and α-agonists3,4 bind to separate and structurally specific sites on neurones in the central1,3 and enteric nervous systems2,4. One functional consequence of this binding is inhibition of cell firing5,6, which may be due to hyperpolarization of the resting membrane by opiates, such as has been observed in the guinea pig locus coeruleus7 and myenteric plexus8, and by clonidine in the myenteric plexus9. However, the discharge frequency of many nerve cells is limited by the membrane hyperpolarization which follows a period of activity, and which is caused by a transient increase in the intracellular calcium concentration leading to the activation of a membrane potassium conductance10. Neurones of the guinea pig myenteric plexus exhibit such a calcium-dependent potassium conductance11–13. We now report that both opiates and clonidine prolong this calcium-dependent after-hyperpolarization at concentrations (100 pM–10 nM) which are considerably lower than those usually required to hyperpolarize the resting membrane. Such a prolongation of the after-hyperpolarization will limit the frequency of discharge of neurones without altering their resting potential. The nature of the effects of morphine and clonidine are of interest in view of the similarities between the anatomical distribution of binding sites for these two drugs and the close parallels between their pharmacological effects in animals and man.
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Tokimasa, T., Morita, K. & North, A. Opiates and clonidine prolong calcium-dependent after-hyperpolarizations. Nature 294, 162–163 (1981). https://doi.org/10.1038/294162a0
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DOI: https://doi.org/10.1038/294162a0
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