The Journal of Neurophysiology Vol. 78 No. 2 August 1997, pp. 780-789
Copyright ©1997 The American Physiological Society

Modulation of Ca²⁺ Currents by Various G Protein-Coupled Receptors in Sympathetic Neurons of Male Rat Pelvic Ganglia

Yu Zhu and Jerrel L. Yakel

Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709

Zhu, Yu and Jerrel L. Yakel. Modulation of Ca²⁺ currents by various G protein-coupled receptors in sympathetic neurons of male rat pelvic ganglia. J. Neurophysiol. 78: 780-789, 1997. The modulation of voltage-gated calcium (Ca²⁺) channels by various G protein-coupled receptor pathways was investigated in sympathetic neurons of the male rat major pelvic ganglion (MPG). Standard whole cell patch-clamp recording techniques were used to record Ca²⁺ currents from acutely dissociated neurons. The activation of muscarinic receptors, which uses a G protein pathway that was not blocked by either pertussis toxin (PTX) or cholera toxin (CTX), inhibited both N-type and L-type Ca²⁺ channels. The activation of ₂ noradrenergic receptors with the selective agonist UK14304, which used primarily a PTX-sensitive G protein pathway, inhibited only N-type Ca²⁺ channels. The activation ofvasoactive intestinal polypeptide (VIP) receptors, which used a CTX-sensitive G protein pathway, also inhibited only N-type Ca²⁺ channels. UK14304 and VIP induced a bell-shaped inhibition of the Ca²⁺ current with a peak inhibition at around +10 mV and decreasing inhibition at more positive potentials. In contrast, the muscarine-induced Ca²⁺ current inhibition was not bell shaped and was more prominent at more positive potentials. Furthermore, a large depolarization, which relieved the current inhibition by UK14304 and VIP, did not relieve the inhibition by muscarine. Besides inhibiting the Ca²⁺ current, UK14304 and VIP also slowed the activation kinetics, an effect not seen with muscarine. Replacing external Ca²⁺ with Ba²⁺ and replacing internal ethylene glycol-bis(-aminoethyl ether)-N,N,N,N-tetraacetic acid (EGTA) with high bis-(o-aminophenoxy)-N,N,N,N-tetraacetic acid (BAPTA) completely blocked the inhibitory effect of muscarine. However, the inhibitory effects of both UK14304 and VIP were unaffected under these conditions. Surprisingly, the facilitation of the Ca²⁺ current was eliminated under these strong calcium-buffering conditions. The activation of protein kinase C (PKC) with phorbol 12-myristate 13-acetate (PMA) increases the amplitude of the Ca²⁺ current, diminishes facilitation, and reduces the inhibition of this current by UK14304 and VIP. However, PKC activation did not reduce the muscarine-induced Ca²⁺ current inhibition. In summary, our data suggest that muscarine uses a mechanism different from UK14304 and VIP to modulate the N-type Ca²⁺ channels in sympathetic neurons of the MPG. Although VIP and UK14304 use different G protein pathways, these two different pathways most likely converge downstream to compete for the same target site on the N-type Ca²⁺ channels.

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