Unique properties of non-N-methyl-D-aspartate excitatory responses in cultured purkinje neurons.
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.
Joels
M
M
Division of Preclinical Neuroscience and Endocrinology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
Yool
A J
AJ
Gruol
D L
DL
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002413:Cations, Divalent; D002794:Choline / Q000494:pharmacology; D004553:Electric Conductivity; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology; D007608:Kainic Acid / Q000494:pharmacology; D007736:Kynurenic Acid / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D016202:N-Methylaspartate; D010069:Oxadiazoles / Q000494:pharmacology; D011689:Purkinje Cells / Q000187:drug effects / Q000502:physiology*; D016318:Quisqualic Acid; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000502:physiology; D012964:Sodium / Q000494:pharmacology; D013395:Sucrose / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D002413:Cations, Divalent; D007473:Ion Channels; D010069:Oxadiazoles; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D002104:Cadmium; D001224:Aspartic Acid; D013779:Tetrodotoxin; D013395:Sucrose; D016202:N-Methylaspartate; D016318:Quisqualic Acid; D012964:Sodium; D007736:Kynurenic Acid; D008274:Magnesium; D002794:Choline; D007608:Kainic Acid; D002118:Calcium