The Journal of Neurophysiology Vol. 80 No. 3 September 1998, pp. 1094-1104
Copyright ©1998 The American Physiological Society

Inhibition of a Hyperpolarization-Activated Current by Clonidine in Rat Dorsal Root Ganglion Neurons

Junichi Yagi^{1, 2} and Rhyuji Sumino²

¹ Department of Physiology, Kyorin University School of Medicine, Tokyo 181-8611; and ² Department of Physiology, Nihon University School of Dentistry, Tokyo 101-0062, Japan

Yagi, Junichi and Rhyuji Sumino. Inhibition of a hyperpolarization-activated current by clonidine in rat dorsal root ganglion neurons. J. Neurophysiol. 80: 1094-1104, 1998. Whole cell voltage- and current-clamp recordings were carried out to investigate the effects of clonidine, an ₂-adrenoceptor agonist, in L₄ and L₅ dorsal root ganglion (DRG) neurons of the rat. In voltage-clamp mode, application of 20 µM clonidine reversibly reduced the inward current evoked by hyperpolarizing voltage steps. The "clonidine-sensitive current" was obtained by subtracting the current during clonidine application from the control current, and its properties were as follows. 1) It was a slowly activating inward current evoked by hyperpolarization. 2) The reversal potential in the standard extracellular solution ([K⁺]_o = 5 mM, [Na⁺]_o = 151 mM) was 38.3 mV, and reduction of [Na⁺]_o shifted it to a more negative potential, whereas an increase of [K⁺]_o shifted it to a more positive potential, indicating that the current was carried by Na⁺ and K⁺ (P_Na/P_K = 0.22). 3) The relationship between the chord conductance underlying the clonidine-sensitive current and voltage could be fitted by a Boltzmann equation. These results indicate that the clonidine-sensitive current corresponds to a hyperpolarization-activated current (I_h), i.e., clonidine inhibits I_h in rat DRG neurons. DRG neurons were classified as small (15.9-32.9 µm diam), medium-sized (33-42.9 µm), and large (43-63.6 µm), and 7 of 19, 24 of 25, and 22 of 22 of these types exhibited I_h with mean ± SE clonidine-induced inhibition values of 36.1 ± 3.5% (n = 7), 43.1 ± 3.7% (n = 24), and 35.1 ± 2.7% (n = 22), respectively. Clonidine application to L4 and L5 DRG neurons excised from rats the sciatic nerves of which had been transected 14-35 days previously (transected DRG neurons) also reduced I_h. In current-clamp mode, 9 of 13 intact and 4 of 6 transected medium-sized DRG neurons that exhibited I_h responded to clonidine with hyperpolarization (>2 mV). Some medium-sized DRG neurons exhibited repetitive action potentials in response to a depolarizing current pulse, and clonidine reduced the firing discharge frequencies in 8 of 11 intact and 3 of 4 transected neurons tested. Injection of a hyperpolarizing current pulse produced time-dependent rectification in DRG neurons that exhibited I_h, and clonidine blocked this rectification in all intact and transected neurons tested. These results suggest that inhibition of I_h due to ₂-adrenoceptor activation contributes to modulation of DRG neuronal activity in rats. On the basis of our findings, we discuss the possible mechanisms whereby sympathetically released norepinephrine modulates the abnormal activity of DRG neuronal cell bodies after nerve injury.

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