Modeling temperature- and Cav3 subtype-dependent alterations in T-type calcium channel mediated burst firing

Molecular Brain

Fernando R. Fernandez¹  Ray W. Turner²  Mircea C. Iftinca³  Gerald W. Zamponi⁴ 

[1] Department of Biomedical Engineering, Boston University, Boston, MA, USA;Department of Cell Biology and Anatomy, Cumming School of Medicine University of Calgary, Calgary, Canada;Hotchkiss Brain Institute, University of Calgary, Calgary, Canada;Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, Canada;Department of Physiology and Pharmacology, Cumming School of Medicine University of Calgary, Calgary, Canada;Hotchkiss Brain Institute, University of Calgary, Calgary, Canada;Department of Physiology and Pharmacology, Cumming School of Medicine University of Calgary, Calgary, Canada;Hotchkiss Brain Institute, University of Calgary, Calgary, Canada;Alberta Children’s Hospital Research Institute, University of Calgary, Calgary, Canada;

关键词: Cav3;    T-type;    Calcium channel;    Rebound burst discharge;    Temperature;   

DOI  :  10.1186/s13041-021-00813-7

来源: Springer

【 摘 要 】

T-type calcium channels are important regulators of neuronal excitability. The mammalian brain expresses three T-type channel isoforms (Cav3.1, Cav3.2 and Cav3.3) with distinct biophysical properties that are critically regulated by temperature. Here, we test the effects of how temperature affects spike output in a reduced firing neuron model expressing specific Cav3 channel isoforms. The modeling data revealed only a minimal effect on baseline spontaneous firing near rest, but a dramatic increase in rebound burst discharge frequency for Cav3.1 compared to Cav3.2 or Cav3.3 due to differences in window current or activation/recovery time constants. The reduced response by Cav3.2 could optimize its activity where it is expressed in peripheral tissues more subject to temperature variations than Cav3.1 or Cav3.3 channels expressed prominently in the brain. These tests thus reveal that aspects of neuronal firing behavior are critically dependent on both temperature and T-type calcium channel subtype.

【 授权许可】

CC BY