The Journal of Neurophysiology Vol. 83 No. 2 February 2000, pp. 791-795
Copyright ©2000 by the American Physiological Society

Effect of High Ba²⁺ on Norepinephrine-Induced Inhibition of N-Type Calcium Current in Bullfrog Sympathetic Neurons

 ¹Department of Physiology, Tulane University Medical School, New Orleans, Louisiana 70112; and  ²Department of Pharmacology, Chonbuk University Dental School, Chonju, Korea 561-756

Lee, Hye Kyung, Lian Liu, and Keith S. Elmslie. Effect of High Ba²⁺ on Norepinephrine-Induced Inhibition of N-Type Calcium Current in Bullfrog Sympathetic Neurons. J. Neurophysiol. 83: 791-795, 2000. The voltage-dependent inhibition of N-type calcium current by neurotransmitters is the best-understood example of neuronal calcium channel inhibition. One of the mechanisms by which this pathway is thought to inhibit the calcium current is by reducing the permeation of divalent cations through the channel. In this study one prediction of this hypothesis was examined, that high concentrations of divalent cations reduce the maximum neurotransmitter-induced inhibition. Norepinephrine (NE)-induced inhibition was compared in external solutions containing either 2 or 100 mM Ba²⁺. Initially, NE dose-response curves were generated by averaging data from many neurons, and it was found that the relationship was right shifted in the high-Ba²⁺ external solution without an effect on maximum inhibition. The IC₅₀ was 0.6 and 3 µM in 2 and 100 mM Ba²⁺, respectively. This shift was verified by comparing the effect of NE on single neurons exposed to both 2 and 100 mM Ba²⁺. The inhibition induced by 1 µM NE was reduced in 100 mM Ba²⁺ compared with that in 2 mM Ba²⁺. However, the response to 100 µM NE was identical between high and low Ba²⁺. Thus, divalent cations appear to act as a competitive inhibitor of NE binding, which likely results from these ions' interacting with negatively charged amino acids that are important for catecholamine binding to adrenergic receptors. Because the maximum inhibition induced by NE was similar in low and high Ba²⁺, the effect of inhibition on single N-type calcium channels was not altered by the divalent cation concentration.