Key result
Increasing temperature to 37°C in a neuronal model increased peak frequency during rebound bursts for all Cav3 isoforms, with Cav3.1 and Cav3.3 showing much larger peak firing frequencies than Cav3.2.
Why the study?
The mammalian brain expresses three T-type channel isoforms with distinct biophysical properties critically regulated by temperature, but how temperature affects spike output across specific isoforms was unclear.
Neuronal firing behavior, specifically rebound burst discharge, is critically dependent on both temperature and the specific T-type calcium channel subtype expressed.
Temperature effects on Cav3 isoforms may alter excitability in disease; modeling leaves open in vivo validation.
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.
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Fernandez et al. (2021) studied Neuronal excitability (computational model). Temperature increase (37°C vs 21°C) and Cav3 subtype expression vs. 21°C was evaluated on Rebound burst discharge frequency. Increasing temperature to 37°C in a neuronal model increased peak frequency during rebound bursts for all Cav3 isoforms, with Cav3.1 and Cav3.3 showing much larger peak firing frequencies than Cav3.2.
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