Epileptiform activity induces distance‐dependent alterations of the Ca²⁺ extrusion mechanism in the apical dendrites of subicular pyramidal neurons

Abstract

The cellular and molecular mechanisms that underlie acquired changes in Ca(2+) dynamics of different neuronal compartments are important in the induction and maintenance of epileptiform activity. Simultaneous electrophysiology and Ca(2+) imaging techniques were used to understand the basic properties of dendritic Ca(2+) signaling in rat subicular pyramidal neurons during epileptiform activity. Distance-dependent changes in the Ca(2+) decay kinetics locked to spontaneous epileptiform discharges and back-propagating action potentials were observed in the apical dendrites. A decrement in the mean tau value of Ca(2+) decay was observed in distal parts (95-110 mum) of the apical dendrites compared with proximal segments (30-45 mum) in in-vitro epileptic conditions but not in control. Pharmacological agents that block Ca(2+) transporters, i.e. Na(+)/ Ca(2+) exchangers (Benzamil), plasma membrane Ca(2+)-ATPase pumps (Calmidazolium) and smooth endoplasmic reticulum Ca(2+)-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 Ca(2+) extrusion mechanisms. The relative contribution of Na(+)/Ca(2+) exchangers in Ca(2+) 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 Ca(2+) homeostatic mechanisms that restore normal Ca(2+) levels could play a major neuroprotective role in the distal dendrites that receive synaptic inputs.

Lactate reduces epileptiform activity through HCA1 and GIRK channel activation in rat subicular neurons in an in vitro model

“…36,37 It produces epileptiform discharges despite the presence of synaptic inhibition. 36,37 It produces epileptiform discharges despite the presence of synaptic inhibition.…”

“…The 4-AP-0Mg 2+ model of epilepsy has been established previously in different regions of the brain including subiculum of the hippocampus. 36,37 It produces epileptiform discharges despite the presence of synaptic inhibition. 38,39 Astrocytes internalize lactate via MCT1/4 but the concentration of the blocker used in our study blocks only neuronal MCT2.…”

Abnormal alterations in the Ca2+/CaV1.2/calmodulin/caMKII signaling pathway in a tremor rat model and in cultured hippocampal neurons exposed to Mg2+-free solution

“…In the present study, the [Ca 2+ ] I fluorescence intensity was increased in the TRMs (hippocampus, temporal cortex and cerebellum) and in the in vitro model, indicating that Ca 2+ mayt be a key element in the epileptogenesis of these two models. [Ca 2+ ] I led to the depolarization of cells, activating the inflow of Na+ and further enhancing epilepsy ( 37 , 38 ). Previous studies demonstrated that status epilepticus causes sustained elevation of intracellular calcium levels in the hippocampal neuronal culture model ( 39 , 40 ).…”

Tonic current through GABAA receptors and hyperpolarization‐activated cyclic nucleotide‐gated channels modulate resonance properties of rat subicular pyramidal neurons

“…Studies on the cellular mechanisms associated with these observations are scarce. Work from our laboratory suggests the up‐regulation of Ca 2+ transporter mechanisms (Srinivas & Sikdar, ) and increased inhibitory synaptic inputs (Sah & Sikdar, ) that may dampen hyperexcitability in these neurons. Quantitative pharmacological analysis performed on subicular GABA A receptors from chronic epilepsy models revealed a significant increase in GABA A receptor‐mediated tonic inhibition (Biagini et al ., ).…”