A Markov model of human Cav2.3 channels and their modulation by Zn2+ (Neumaier et al 2020)


The Markov model for Cav2.3 channel gating in the absence of trace metals was developed based on channel structure, previous modeling studies and the ability to fit the data. Model parameters were optimized by fitting the model to macroscopic currents recorded with various electrophysiological protocols from HEK-293 cells stably transfected with human Cav2.3+ß3 channel subunits. The effects of Zn2+ were implemented by assuming that Zn2+ binding to a first site (KZn=0.003 mM) leads to electrostatic modification and mechanical slowing of one of the voltage-sensors while Zn2+-binding to a second, intra-pore site (KZn=0.1 mM) blocks the channel and modifies the opening and closing transitions.

Model Type: Channel/Receptor

Region(s) or Organism(s): Human

Currents: I Calcium

Model Concept(s): Markov-type model; Ion Channel Kinetics; Simplified Models; Drug binding

Simulation Environment: NEURON

References:

Neumaier F, Alpdogan S, Hescheler J, Schneider T. (2020). Zn2+-induced changes in Cav2.3 channel function: An electrophysiological and modeling study The Journal of general physiology. 152 [PubMed]


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