Journal of Neurophysiology, Vol 69, Issue 4 1060-1070, Copyright © 1993 by APS

ARTICLES

Alpha-adrenergic modulation of ionic currents in cultured parasympathetic neurons from rat intracardiac ganglia

Z. J. Xu and D. J. Adams
Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, Florida 33101.

1. Modulation of ionic conductances by alpha-adrenergic agonists was investigated in cultured parasympathetic neurons from rat intracardiac ganglia. Application of norepinephrine (NE, 25-100 microM) to the soma of isolated neurons reversibly reduced both the amplitude and duration of the Ca(2+)-dependent action potential evoked by injection of depolarizing current when Na+ and K+ currents were blocked pharmacologically. 2. In the whole-cell voltage-clamp mode, application of NE reversibly reduced the amplitude and rate of activation of Ca2+ current (ICa). The amplitude inhibition was greater at the peak of the current (55%) than at the end of a 700-ms pulse (20%). Maximal doses of NE produced only approximately 60% inhibition of peak ICa amplitude. 3. Inactivation of ICa was best fit by the sum of two exponential functions in the absence of NE, but was described by a single exponential function in the presence of NE. These results suggest that NE preferentially inhibited a fast inactivating component of the Ca2+ current in these parasympathetic neurons. 4. NE reversibly reduced the amplitude of Ba2+ tail currents through open Ca channels at all voltages from -40 to +150 mV with a slight shift in the activation curve determined from the current-voltage (I-V) relationship for the tail currents. NE did not change the voltage dependence of the steady-state inactivation of the calcium channels. 5. NE inhibited Ca2+ current either in the absence or presence of nifedipine but to a lesser extent in the presence of omega-conotoxin (omega-CGTX), suggesting that the Ca channels inhibited by NE are predominantly omega-CGTX sensitive. 6. The inhibition of ICa by NE was mimicked by the alpha 1-adrenergic agonists methoxamine and phenylephrine and potentiated in the presence of the alpha 2-adrenoceptor antagonist yohimbine (10 microM). NE inhibition of ICa was antagonized by bath application of the alpha-adrenergic antagonist phentolamine (1 microM), but not by prazosin (1-10 microM), yohimbine, or the beta-adrenergic antagonist propranolol (1 microM). Taken together, these results suggest that NE inhibition of Ca2+ current in rat parasympathetic cardiac neurons is mediated by an alpha-adrenergic receptor with properties that may differ from alpha 1- and alpha 2-adrenoceptors. 7. In approximately 35% of neurons studied, NE not only reduced depolarization-activated inward Ca2+ current but also increased an outward current, with a shift of the I-V curve and reversal potential to more negative voltages.(ABSTRACT TRUNCATED AT 400 WORDS)

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