CLONIDINE REDUCES HYPERPOLARIZATION-ACTIVATED INWARD CURRENT (I-H) INRAT HYPOGLOSSAL MOTONEURONS

We used intracellular recording techniques to investigate the actions of clonidine on hypoglossal motoneurons (HMs) in rat brainstem slices. Clonidine (10-100 mu M) produced a small (2-6 mV), dose-dependent hyp erpolarization in HMs, accompanied by an increase in peak input resist ance (RN). It also slowed the time course of the depolarizing 'sag' of the voltage response to constant hyperpolarizing current steps. These effects were mimicked by the alpha(2)-adrenoceptor (alpha(2)-AR) agon ist guanabenz, but not by the I-1-imidazoline receptor agonists moxoni dine or rilmenidine. Recorded in single-electrode voltage clamp mode, clonidine decreased input conductance of HMs and reduced the amplitude of a hyperpolarization-activated inward current (I-h). Clonidine's ef fect on I-h was three-fold: it shifted the half-activation voltage (V- 1/2) in the hyperpolarizing direction (by 4.4 +/- 0.7 mV at a dose of 10 mu M), decreased the maximal current (by similar to 20%), and slowe d the time course of I-h activation at all voltage steps. At the most hyperpolarized potential steps, clonidine slowed activation of I-h dra matically, yielding a striking increase in the activation time constan t. The alpha(2)-AR antagonists yohimbine and idazoxan reduced clonidin e's effect on V-1/2 and on the I-h activation time course, but neither blocked clonidine's reduction of the maximal current, nor its strong slowing of I-h activation at the most hyperpolarized steps. We were un able to mimic or occlude clonidine's actions with the adenylate cyclas e inhibitor SQ 22536 nor with the non-specific protein kinase inhibito r H-7. We conclude that clonidine hyperpolarizes HMs via a reduction o f the amount of I-h that is active at rest, and that the response is m ediated in part by alpha(2)-ARs. Some effects of clonidine on these ne urons do not appear to be receptor-mediated, and may be due to physica l block by clonidine of I-h channels. (C) 1997 Elsevier Science B.V.