The Journal of Neurophysiology Vol. 79 No. 2 February 1998, pp. 583-594
Copyright ©1998 The American Physiological Society

Voltage-Dependent Calcium Currents in Bulbospinal Neurons of Neonatal Rat Rostral Ventrolateral Medulla: Modulation by ₂-Adrenergic Receptors

Yu-Wen Li, Patrice G. Guyenet, and Douglas A. Bayliss

Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908

Li, Yu-Wen, Patrice G. Guyenet, and Douglas A. Bayliss. Voltage-dependent calcium currents in bulbospinal neurons of neonatal rat rostral ventrolateral medulla: modulation by ₂-adrenergic receptors. J. Neurophysiol. 79: 583-594, 1998. The properties and modulation by norepinephrine (NE) of voltage-dependent calcium currents were studied in bulbospinal neurons (n = 116) of the rostral ventrolateral medulla (RVLM) using whole cell patch-clamp techniques in neonatal rat brain stem slices. RVLM bulbospinal neurons were identified visually by their location in slices and by the presence of flourescein isothiocyanate-tagged microbeads, which were injected into the spinal cord before the experiment; RVLM neurons were filled with Lucifer yellow during recordings, and the slice was processed for detection of tyrosine hydroxylase immunoreactivity (TH-IR). Thirty-four of 42 recovered cells (81%) were positive for TH-IR, indicating that most recorded cells were C1 neurons. Bulbospinal RVLM neurons expressed a prominent high-voltage-activated (HVA) calcium current, which began to activate at 30 to 40 mV (from a holding potential of 60 or 70 mV), and peaked at ~0 mV (0.8 ± 0.1 nA;mean ± SE). HVA current comprised predominantly -conotoxin GVIA-sensitive, N-type and -agatoxin IVA-sensitive, P/Q-type components, with smaller dihydropyridine-sensitive, L-type, and residual current components. Most RVLM bulbospinal neurons (n = 44/52, including 12/14 histologically identified C1 cells) also expressed low-voltage-activated (LVA) calcium current. LVA current began to activate at ~60 mV (from a holding potential of 100 mV) and was nearly completely inactivated at 50 mV with a half-inactivation potential of 70 ± 2 mV. The amplitude of LVA current at 50 mV was 78 ± 24 pA with Ba²⁺ and 156 ± 38 pA with Ca²⁺ as a charge carrier. NE inhibited HVA current in most bulbospinal RVLM neurons (n = 70/77) with an EC₅₀ of 1.2 µM; NE had no effect on LVA current. Calcium current inhibition by NE was mediated by ₂-adrenergic receptors (₂-ARs) as the effect was mimicked by the selective ₂-AR agonist, UK-14,304, and blocked by idazoxan, an ₂-AR antagonist, but unaffected by prazosin and propranolol (₁- and -AR antagonists, respectively). Most of the NE-sensitive calcium current was N- and P/Q-type. NE-induced inhibition of calcium current evoked by action potential waveforms (APWs) was significantly larger than that evoked by depolarizing steps (34 ± 2.5 vs. 23 ± 2.7%; P < 0.05). Although inhibition of calcium current was voltage dependent and partially relieved by strong depolarizations, when calcium currents were evoked with a 10-Hz train of APWs as a voltage command, the inhibitory effect of NE was maintained throughout the train. In conclusion, bulbospinal RVLM neurons, including C1 cells, express multiple types of calcium currents. Inhibition of HVA calcium current by NE may modulate input-output relationships and release of transmitters from C1 cells.

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