Clustering of L-type Ca²⁺ channels at the base of major dendrites in hippocampal pyramidal neurons

Abstract

INTEGRATION and processing of electrical signals in individual neurons depend critically on the spatial distribution of ion channels on the cell surface. In hippocampal pyramidal neurons, voltage-sensitive calcium channels have important roles in the control of Ca²⁺-dependent cellular processes such as action potential generation^1,2, neurotransmitter release³, and epileptogenesis^4,5. Long-term potentiation of synaptic transmission in the hippocampal pyramidal cell, a form of neuronal plasticity that is thought to represent a cellular correlate of learning and memory^6,7, is dependent on Ca²⁺ entry mediated by synaptic activation of glutamate receptors that have a high affinity for NMDA (JV-methyl(-D-aspartate) and are located in distal dendrites^8,9. Stimuli causing long-term potentiation at these distal synapses also cause a large local increase in cytosolic Ca²⁺ in the proximal regions of dendrites¹⁰. This increase has been proposed to result from activation of voltage-gated Ca²⁺ channels¹⁰. At least four types of voltage-gated Ca²⁺ channels, designated N, L, T and P (refs 11, 12), may be involved in these processes. Here we show that L-type Ca²⁺channels, visualized using a monoclonal antibody, are located in the cell bodies and proximal dendrites of hippocampal pyramidal cells and are clustered in high density at the base of major dendrites. We suggest that these high densities of L-type Ca²⁺channels may serve to mediate Ca²⁺ entry into the pyramidal cell body and proximal dendrites in response to summed excitatory inputs to the distal dendrites and to initiate intracellular regulatory events in the cell body in response to the same synaptic inputs that cause long-term potentiation at distal dendritic synapses.