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Selective tuning of L-type voltage-sensitive calcium channels to strong synaptic activity

University of British Columbia

L-type voltage-sensitive Ca²⁺ channels VSCCs are important in mediating activity-dependent gene expression that may contribute to neuronal plasticity. Evidence shows that the L-type VSCC has slow activation kinetics making it function as a filter'for action potentials and therefore respond more effectively to the long-lasting EPSP waveform. However, these results are derived from experiments performed at room temperature and need to be tested at physiological temperature. Moreover, whether the square pulse analysis is legitimate for calcium channel behavior in the complex synaptic depolarization - waveform remains unclear. Using existing waveforms modeled from the 'NEURON' simulation program, we tested our hypothesis that at physiological temperature, slow activation kinetics underlie the L-type VSCCs' preference for EPSP type waveforms over action potential type waveforms. Different simulated waveforms were used as voltage clamp commands to HEK cells with heterologously expressed calcium channels, along with regular step pulses for basic channel property analysis. Our results show that activation kinetics are drastically accelerated compared to that obtained at room temperature such that all three channel types, L-, P/Q- and N-type channels are equally activated to full scale by action potentials. The L-type VSCCs mediate a distinctively larger total calcium influx in response to strong synaptic inputs in comparison with the P/Q- and N-type channels. Further analysis indicates that inactivation rather than activation characteristics underlies the distinctive Ltype calcium current response to strong synaptic inputs at physiological temperature. In summary, this inactivation-dominated behavior tunes the Ltype calcium channels to the strong synaptic inputs that may be important in triggering gene expression.

Thesis/Dissertation

application/pdf

2009-09-15

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http://hdl.handle.net/2429/12754

Neuroscience

University of British Columbia

UBCV

DSpace