A hyperpolarizing response induced by glutamate in mouse cerebellar Purkinje cells

In the vertebrate nervous system, glutamate (Glu) receptors are generally known to cause depolarizing responses. We report here a novel type of Glu response in Purkinje neurons of mouse cerebellar slices, namely glutamate-induced hyperpolarization (GH). This response is not due to activation of inhibitory interneurons, because application of tetrodotoxin (TTX), bicuculline, or strychnine did not abolish GH. In addition, GH persisted in a Ca²⁺-free or a low-Cl^- solution, which rules out the involvement of g_K(Ca) or GABA_A mechanisms. Quisqualate (Quis) and trans-1-amino-1,3-cyclopentanedicarboxylic acid (tACPD), which are potent and selective agonists, respectively, for the metabotropic Glu receptor (mGluR), failed to induce GH. l-2-Amino-4-phosphonobutyric acid (l-AP4) was also ineffective. Simultaneous recording of electrical activity and intracellular Ca²⁺ concentration ([Ca²⁺]_i) showed that GH was not accompanied by [Ca²⁺]_i changes. Voltage clamp experiments showed that GH is due to reduction of a tonically active conductance with a reversal potential around 0 mV. Two possible mechanisms are suggested for GH: (1) changes in the desensitized steady state of ionotropic Glu receptors, or (2) a novel Glu-mediated mechanism.