Clustering of L-type Ca2+ channels at the base of major dendrites in hippocampal pyramidal neurons.
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, neurotransmitter release, and epileptogenesis. 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, is dependent on Ca2+ entry mediated by synaptic activation of glutamate receptors that have a high affinity for NMDA (N-methyl(-D-aspartate) and are located in distal dendrites. Stimuli causing long-term potentiation at these distal synapses also cause a large local increase in cytosolic Ca2+ in the proximal regions of dendrites. This increase has been proposed to result from activation of voltage-gated Ca2+ channels. At least four types of voltage-gated Ca2+ channels, designated N, L. T and P, 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.
Westenbroek
R E
RE
Department of Pharmacology, School of Medicine, University of Washington, Seattle 98195.
Ahlijanian
M K
MK
Catterall
W A
WA
D000818:Animals; D000911:Antibodies, Monoclonal; D015220:Calcium Channels / Q000032:analysis* / Q000502:physiology; D003712:Dendrites / Q000032:analysis*; D004095:Dihydropyridines / Q000494:pharmacology; D006624:Hippocampus / Q000648:ultrastructure*; D007124:Immunoenzyme Techniques; D007163:Immunosorbent Techniques; D017275:Isradipine; D009474:Neurons / Q000648:ultrastructure*; D010069:Oxadiazoles / Q000378:metabolism; D010456:Peptides, Cyclic / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013570:Synaptic Membranes / Q000032:analysis; D020960:omega-Conotoxins
D000911:Antibodies, Monoclonal; D015220:Calcium Channels; D004095:Dihydropyridines; D010069:Oxadiazoles; D010456:Peptides, Cyclic; D020960:omega-Conotoxins; C053423:Conus magus toxin; C038806:1,4-dihydropyridine; D017275:Isradipine