Summary: | Evidence suggests an important role for L-type voltage sensitive Ca + channels
(VSCCs) in activating immediate early genes (Murphy et al. 1991). To understand how
L-type VSCCs regulate somatic and nuclear Ca2 + dynamics in response to different
synaptic bursting waveforms that might be associated with unique forms of plasticity, we
have modeled hippocampal CA1 neuron electrophysiology and intracellular Ca2+
dynamics. The model reproduces most of the eletrophysiological properties of
hippocampal CA1 neurons, such as bursting vs. nonbursting behavior, AP frequency
accommodation and AP back propagation. We examined Ca²⁺ influx through L-type
VSCCs, and the resulting intracellular Ca²⁺ transient in response to simulated waveforms
obtained with different presynaptic firing frequencies, active conductances and synaptic
conductances. Simulation results suggest that L-type VSCCs prefer synaptic stimuli and
conditions that result in a high depolarization plateau over other types of waveforms
including repetitive APs, subthreshold EPSPs, or bursting firing. It was found that low
activation potential and slow activation rate of L-type VSCCs contribute to the selective
response of L-type VSCCs to firing patterns.
Pharmacological experiments and simulation results suggest an important role of
intracellular Ca²⁺ stores in nuclear Ca²⁺ elevation in response to either single AP or
tetanic synaptic stimulus. Moreover, previous studies in muscle suggest a specific spatial
relationship between the L-type VSCCs and the ryanodine receptor. Therefore, we sought
to determine whether a similar coupling between Ca²⁺ channels and stores would
facilitate Ca²⁺-induced Ca²⁺ release (CICR) action. Moving the Ca²⁺ stores away from the
Ca²⁺ channels (from 50 nm to 2 μm) resulted in a large reduction in the elevation of Ca²⁺ transient. === Medicine, Faculty of === Graduate
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