Alpha‐adrenergic inhibition of rat cerebellar Purkinje cells in vitro: a voltage‐clamp study.

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Abstract
1. The effects of the alpha 2-adrenergic agonist clonidine on the membrane properties of Purkinje cells were analysed in sagittal slices of adult rat cerebellum by the use of intracellular recordings performed at a somatic level in the single-electrode voltage-clamp mode. 2. In preliminary current-clamp experiments, clonidine elicited in all cells a hyperpolarization 3-8 mV in amplitude, accompanied by a 15-35% increase of the input resistance when it was added to the bath at a concentration of 2-5 microM. 3. In voltage-clamped cells at a potential of -65 mV. the same concentration of clonidine always induced an outward shift of the holding current (0.2-0.5 nA in amplitude), thus corresponding to the hyperpolarization seen in current-clamp experiments, and this effect was accompanied by a clear increase of membrane resistance. Furthermore, clonidine markedly depressed the inward relaxations induced by hyperpolarizing commands of amplitude less than 10-20 mV whereas those induced by larger steps were much less affected. All these effects of clonidine were reversible when the drug was washed out. 4. When the slices were bathed in a medium containing 10 mM-Cs and 5 X 10(-6) M-tetrodotoxin, the inward relaxations induced by hyperpolarizing steps were abolished. However, a small inward current was still present when the membrane potential was stepped back to -65 mV, which was in turn blocked by the Ca-channel blocker Cd. This inward Ca current was also blocked by 2-5 microM-clonidine in the bath. 5. All these effects of clonidine were abolished by the alpha 1-adrenergic antagonists prazosin and phentolamine at concentrations of 0.5 and 40 microM respectively in the bath. In contrast, they were only weakly antagonized or unaffected by 2 microM of the alpha 2-adrenergic antagonist yohimbine. 6. On the basis of these results and of a previous work on the ionic basis of the inward rectification of Purkinje cells (Crepel & Penit-Soria, 1986), it appears that these neurones exhibit a well developed alpha (possibly alpha 1)-adrenergic inhibition of a low-threshold Ca conductance and a Ca-dependent K conductance operating near resting potential.