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Cholinergic stimulation enhances cytosolic calcium ion accumulation in mouse hippocampal CA1 pyramidal neurones during short action potential trains
Author(s) -
Beier Steven M.,
Barish Michael E.
Publication year - 2000
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2000.00129.x
Subject(s) - carbachol , cholinergic , chemistry , hippocampal formation , endocrinology , acetylcholine , calcium , medicine , postsynaptic potential , biophysics , stimulation , biology , receptor , biochemistry , organic chemistry
1 Acetylcholine is a regulatory cofactor for numerous activity‐dependent processes of central nervous system development and plasticity in which increases in cytosolic calcium ion concentration ([Ca 2+ ] cyto ) couple membrane excitation to cellular changes. We examined how cholinergic receptor activation affects temporal and spatial aspects of increases in [Ca 2+ ] cyto during short trains of action potentials in hippocampal CA1 pyramidal neurones. Membrane‐impermeant Ca 2+ ‐sensitive dye was introduced into the cytosol during whole‐cell recordings, and Ca 2+ ‐dependent fluorescence was recorded from somatic, nuclear and proximal dendrite regions with high temporal resolution. 2 In all neuronal compartments, the cholinergic agonist carbachol (5 μM) increased resting [Ca 2+ ] cyto and the maximum [Ca 2+ ] cyto attained during a short action potential train. Carbachol also slowed the recovery of [Ca 2+ ] cyto towards resting levels. The largest increases in peak cytosolic Ca 2+ concentration (Δ[Ca 2+ ] cyto ) were seen in the dendrite and apical cell body, while relaxations of the carbachol‐induced increase in Δ[Ca 2+ ] cyto showed greater prolongation in the nucleus and basal cell body. 3 Most significantly, the difference between Ca 2+ signals recorded before and during exposure to carbachol consistently showed a monotonic rise and smooth fall in all cell compartments, suggesting that the increase in [Ca 2+ ] cyto associated with each action potential was not altered by carbachol. Consistent with this view, changes in Ca 2+ signalling were not accompanied by changes in action potential waveforms. 4 The effects of carbachol were partially reversed by simultaneous exposure to atropine, or partially inhibited by inclusion of heparin in the intracellular solution, indicating the involvement of muscarinic acetylcholine receptors and Ins P 3 ‐sensitive Ca 2+ ‐release channels. 5 Our data indicate that carbachol‐induced slowing of [Ca 2+ ] cyto relaxations after each action potential results in enhanced accumulation of Ca 2+ in the cytosol in the absence of changes in action potential‐driven Ca 2+ entry. By modulating the time course of Ca 2+ signals, cholinergic stimulation may regulate the activation of Ca 2+ ‐dependent intracellular processes dependent on patterns of [Ca 2+ ] cyto changes.