Group I mGluR Activation Causes Voltage-Dependent and -Independent Ca2+Rises in Hippocampal Pyramidal Cells

Abstract

Group I mGluR activation causes voltage-dependent and -independent Ca²⁺rises in hippocampal pyramidal cells. Application of the metabotropic glutamate receptor (mGluR) agonist (1 S,3 R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) or the selective group I mGluR agonist ( S)-3,5-dihydroxyphenylglycine (DHPG) depolarized both CA3 and CA1 pyramidal cells in guinea pig hippocampal slices. Simultaneous recordings of voltage and intracellular Ca²⁺levels revealed that the depolarization was accompanied by a biphasic elevation of intracellular Ca²⁺concentration ([Ca²⁺]_i): a transient calcium rise followed by a delayed, sustained elevation. The transient [Ca²⁺]_irise was independent of the membrane potential and was blocked when caffeine was added to the perfusing solution. The sustained [Ca²⁺]_irise appeared when membrane depolarization reached threshold for voltage-gated Ca²⁺influx and was suppressed by membrane hyperpolarization. The depolarization was associated with an increased input resistance and persisted when either the transient or sustained [Ca²⁺]_iresponses was blocked. mGluR-mediated voltage and [Ca²⁺]_iresponses were blocked by (+)-α-methyl-4-carboxyphenylglycine (MCPG) or ( S)-4-carboxy-3-hydroxyphenylglycine (4C3HPG). These data suggest that in both CA3 and CA1 hippocampal cells, activation of group I mGluRs produced a biphasic accumulation of [Ca²⁺]_ivia two paths: a transient release from intracellular stores, and subsequently, by influx through voltage-gated Ca²⁺channels. The concurrent mGluR-induced membrane depolarization was not caused by the [Ca²⁺]_irise.