Neurological phenotype and synaptic function in mice lacking the Ca V1.3 α subunit of neuronal L-type voltage-dependent Ca 2+ channels

Abstract

Neuronal L-type calcium channels have been implicated in pain perception and neuronal synaptic plasticity. To investigate this we have examined the effect of disrupting the gene encoding the Ca V1.3 (α1D) α subunit of L-type Ca 2+ channels on neurological function, acute nociceptive behavior, and hippocampal synaptic function in mice. Ca V1.3 α1 subunit knockout (Ca V1.3α1 −/−) mice had relatively normal neurological function with the exception of reduced auditory evoked behavioral responses and lower body weight. Baseline thermal and mechanical thresholds were unaltered in these animals. Ca V1.3α1 −/− mice were also examined for differences in N-methyl- d-aspartate (NMDA) receptor-dependent (100 Hz tetanization for 1 s) and NMDA receptor-independent (200 Hz in 100 μM DL-2-amino-5-phosphopentanoic acid) long-term potentiation within the CA1 region of the hippocampus. Both NMDA receptor-dependent and NMDA receptor-independent forms of long-term potentiation were expressed normally. Radioligand binding studies revealed that the density of (+)[ 3H]isradipine binding sites in brain homogenates was reduced by 20–25% in Ca V1.3α1 −/− mice, without any detectable change in Ca V1.2 (α1C) protein levels as detected using Western blot analysis. Taken together these data indicate that following loss of Ca V1.3α1 subunit expression there is sufficient residual activity of other Ca 2+ channel subtypes to support NMDA receptor-independent long-term potentiation and some forms of sensory behavior/function.