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

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. © 1987 The Physiological Society