Epileptiform activity induces distance‐dependent alterations of the Ca2+ extrusion mechanism in the apical dendrites of subicular pyramidal neurons |
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Authors: | Kalyan V. Srinivas Sujit K. Sikdar |
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Affiliation: | Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560 012, India |
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Abstract: | The cellular and molecular mechanisms that underlie acquired changes in Ca2+ dynamics of different neuronal compartments are important in the induction and maintenance of epileptiform activity. Simultaneous electrophysiology and Ca2+ imaging techniques were used to understand the basic properties of dendritic Ca2+ signaling in rat subicular pyramidal neurons during epileptiform activity. Distance‐dependent changes in the Ca2+ decay kinetics locked to spontaneous epileptiform discharges and back‐propagating action potentials were observed in the apical dendrites. A decrement in the mean τ value of Ca2+ decay was observed in distal parts (95–110 μm) of the apical dendrites compared with proximal segments (30–45 μm) in in‐vitro epileptic conditions but not in control. Pharmacological agents that block Ca2+ transporters, i.e. Na+/ Ca2+ exchangers (Benzamil), plasma membrane Ca2+‐ATPase pumps (Calmidazolium) and smooth endoplasmic reticulum Ca2+‐ATPase pumps (Thapsigargin), were applied locally to the proximal and distal part of the apical dendrites in both experimental conditions to understand the molecular aspects of the Ca2+ extrusion mechanisms. The relative contribution of Na+/Ca2+ exchangers in Ca2+ extrusion was higher in the distal apical dendrites in the in‐vitro epileptic condition and this property modulated the excitability of the neuron in simulation. The Ca2+ homeostatic mechanisms that restore normal Ca2+ levels could play a major neuroprotective role in the distal dendrites that receive synaptic inputs. |
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Keywords: | Ca2+ extrusion Ca2+ imaging epileptiform activity Na+/Ca2+ exchangers rat subiculum |
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