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. 1989 May;86(9):3404–3408. doi: 10.1073/pnas.86.9.3404

Unique properties of non-N-methyl-D-aspartate excitatory responses in cultured purkinje neurons.

M Joels 1, A J Yool 1, D L Gruol 1
PMCID: PMC287141  PMID: 2470102

Abstract

Cerebellar Purkinje neurons respond to glutamate and to the agonists quisqualate (QA) and kainate (KA) with prolonged, multiphasic, voltage-dependent depolarizations. In contrast, N-methyl-D-aspartate (NMDA) at equivalent doses is not effective as an agonist for Purkinje neurons. The responses to QA and KA are reduced by extracellular Cd2+ (30 microM), by increased Mg2+ or Ca2+ (12 mM), and by the glutamate antagonist kynurenic acid (1 mM) but not by the NMDA-selective antagonist 2-amino-5-phosphonovalerate (100 microM). The short pressure application of 1 microM QA (less than or equal to 0.5 s) produces a response often exceeding 1 min in duration, which consists of several phases: rapid initial depolarization, followed by a long plateau, repolarization, and a subsequent small hyperpolarization. A similar response is evoked by glutamate and KA at higher doses (30-50 microM). The initial and plateau depolarizations are dependent on Na+, being reduced by substitution of external Na+ with sucrose or choline, but are not affected by the Na+ channel blocker tetrodotoxin. Rectification, observed at hyperpolarized potentials below -60 mV set by current clamp, is attributed in part to an intrinsic voltage sensitivity of the agonist-activated response. Both the duration and the magnitude of the excitatory responses were found to be voltage-dependent. Single-channel recordings of a Ca2+-sensitive K+ channel, activated selectively during the excitatory response, suggest that intracellular Ca2+ increases during the plateau phase. Certain properties of the excitatory responses in the Purkinje neuron resemble those associated with NMDA-receptor activation in other regions of the central nervous system, including voltage-sensitive rectification, blockade by divalent cations, and the induction of increased intracellular Ca2+ during the excitatory response. These unique properties may enable the Purkinje neuron to express both rapid and long-term effects of glutamatergic transmission with non-NMDA receptors alone.

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Selected References

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