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

Bianchi, Riccardo, Steven Young, and Robert K. S. Wong. Group I mGluR activation causes voltage-dependent and -independent Ca rises in hippocampal pyramidal cells. J. Neurophysiol. 81: 2903–2913, 1999. Application of the metabotropic glutamate receptor (mGluR) agonist (1S,3R)-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 Ca levels revealed that the depolarization was accompanied by a biphasic elevation of intracellular Ca concentration ([Ca]i): a transient calcium rise followed by a delayed, sustained elevation. The transient [Ca]i rise was independent of the membrane potential and was blocked when caffeine was added to the perfusing solution. The sustained [Ca]i rise appeared when membrane depolarization reached threshold for voltage-gated Ca influx and was suppressed by membrane hyperpolarization. The depolarization was associated with an increased input resistance and persisted when either the transient or sustained [Ca]i responses was blocked. mGluR-mediated voltage and [Ca]i responses were blocked by (1)-a-methyl-4-carboxyphenylglycine (MCPG) or (S)-4-carboxy-3hydroxyphenylglycine (4C3HPG). These data suggest that in both CA3 and CA1 hippocampal cells, activation of group I mGluRs produced a biphasic accumulation of [Ca]i via two paths: a transient release from intracellular stores, and subsequently, by influx through voltage-gated Ca channels. The concurrent mGluR-induced membrane depolarization was not caused by the [Ca]i rise.