The Journal of Neurophysiology Vol. 79 No. 2 February 1998, pp. 753-762
Copyright ©1998 The American Physiological Society

Opioid Receptor-Mediated Inhibition of -Conotoxin GVIA-Sensitive Calcium Channel Currents in Rat Intracardiac Neurons

David J. Adams and Carlo Trequattrini

Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Miami, Florida 33101; and Department of Physiology and Pharmacology, University of Queensland, Brisbane, Queensland 4072, Australia

Adams, David J. and Carlo Trequattrini. Opioid receptor-mediated inhibition of -conotoxin GVIA-sensitive calcium channel currents in rat intracardiac neurons. J. Neurophysiol. 79: 753-762, 1998. Modulation of depolarization-activated ionic conductances by opioid receptor agonists was investigated in isolated parasympathetic neurons from neonatal rat intracardiac ganglia by using the whole cell perforated patch clamp technique. Met-enkephalin (10 µM) altered the action potential waveform, reducing the maximum amplitude and slowing the rate of rise and repolarization but the afterhyperpolarization was not appreciably altered. Under voltage clamp, 10 µM Met-enkephalin selectively and reversibly inhibited the peak amplitude of high-voltage-activated Ca²⁺ channel currents elicited at 0 mV by ~52% and increased three- to fourfold the time to peak. Met-enkephalin had no effect on the voltage dependence of steady-state inactivation but shifted the voltage dependence of activation to more positive membrane potentials whereby stronger depolarization was required to open Ca²⁺ channels. Half-maximal inhibition of Ba²⁺ current (I_Ba) amplitude was obtained with 270 nM Met-enkephalin or Leu-enkephalin. The opioid receptor subtype selective agonists, DAMGO and DADLE, but not DPDPE, inhibited I_Ba and were antagonized by the opioid receptor antagonists, naloxone and naltrindole with IC₅₀s of 84 nM and 1 µM, respectively. The -opioid receptor agonists, bremazocine and dynorphin A, did not affect Ca²⁺ channel current amplitude or kinetics. Taken together, these data suggest that enkephalin-induced inhibition of Ca²⁺ channels in rat intracardiac neurons is mediated primarily by the µ-opioid receptor type. Addition of Met-enkephalin after exposure to 300 nM -conotoxin GVIA, which blocked ~75% of the total Ca²⁺ channel current, failed to cause a further decrease of the residual current. Met-enkephalin inhibited the -conotoxin GVIA-sensitive but not the -conotoxin-insensitive I_Ba in rat intracardiac neurons. Dialysis of the cell with a GTP-free intracellular solution or preincubation of the neurons in Pertussis toxin (PTX) abolished the attenuation of I_Ba by Met-enkephalin, suggesting the involvement of a PTX-sensitive Gprotein in the signal transduction pathway. The activation of µ-opioid receptors and subsequent inhibition of N-type Ca²⁺ channels in the soma and terminals of postganglionic intracardiac neurons is likely to inhibit the release of ACh and thereby regulate vagal transmission to the mammalian heart.

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