The Journal of Neurophysiology Vol. 78 No. 4 October 1997, pp. 1890-1902
Copyright ©1997 The American Physiological Society

Passive and Active Membrane Properties of Isolated Rat Intracardiac Neurons: Regulation by H- and M-Currents

J. Cuevas, A. A. Harper, C. Trequattrini, and D. J. Adams

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

Cuevas, J., A. A. Harper, C. Trequattrini, and D. J. Adams. Passive and active membrane properties of isolated rat intracardiac neurons: regulation by H- and M-currents. J. Neurophysiol. 78: 1890-1902, 1997. The electrical characteristics of isolated neonatal rat intracardiac neurons were examined at 22 and 37°C using the perforated-patch whole cell recording technique. The mean resting membrane potential was 52.0 mV at 37°C and exhibited no temperature dependence. Lowering the temperature from 37 to 22°C decreased the mean input resistance from 854 to 345 M, respectively, and reduced the membrane time constant approximately threefold yielding a Q₁₀ of 2.1. Hyperpolarizing current pulses induced time-dependent rectification of the voltage response in all neurons at both temperatures. This behavior was previously not observed in dialyzed neurons and was reversibly blocked by external Cs⁺ (2 mM) but not Ba²⁺ (1 mM). Voltage-clamp studies of isolated neurons revealed a hyperpolarization-activated inward current. This inwardly rectifying conductance was isolated from other membrane currents using external Cs⁺. The time and voltage dependence of this current is consistent with I_h and contributes to the passive electrical properties of rat intracardiac neurons. In >90% of the neurons studied, depolarizing currents evoked firing of multiple, adapting, action potentials at 22°C. The number of action potentials increased with current strength producing a mean discharge of 5.1 (+100 pA, 1 s pulse), which was attenuated at 37°C to a mean of 1.4. The amplitude and kinetics of the slow, muscarine-sensitive inward and outward currents (I_M) were highly temperature dependent. Lowering the temperature from 37 to 22°C reduced the steady-state current amplitude by approximately one-third and the rate of deactivation of I_M by six- to ninefold at all voltages examined. The average Q₁₀ for the time constant of deactivation of I_M was 3.7 ± 0.3 (mean ± SE). Acetylcholine (ACh) induced tonic discharges in response to depolarizing currents (+100 pA, 1 s pulse) at both temperatures. This effect of ACh was inhibited by the muscarinic receptor antagonists, pirenzepine (100 nM), and mL-toxin (60 nM). At 37°C, a mean discharge of 1.5 was increased to 23.5 in the presence of ACh. A similar switch from phasic to tonic discharge was also produced by the potassium channel inhibitors, Ba²⁺ (1 mM) and uridine-5-triphosphate (UTP; 100 µM), whereas cadmium, 4-aminopyridine, apamin, charybdotoxin, and dendrotoxin did not alter discharge activity. The pharmacological sensitivity profile and temperature dependence of the active membrane properties are consistent with the muscarine-sensitive potassium current (I_M) regulating the discharge activity in rat intracardiac neurons.

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