Calcium currents in hippocampal neurons from kelch-like 1 protein (KLHL1) knockout mice

PERISSINOTTI PP; HE Y; KOOB MD; PIEDRAS-RENTERÍA ES

New Orleans

Congreso; Society for Neuroscience; 2012

KLHL1 is a constitutive neuronal actin-binding protein that up-regulates neuronal HVA calcium currents (CaV2.1 or P/Q-type alpha 1A, and at least one other HVA current component) and LVA currents (CaV3.2 or T-type alpha 1H currents). Here we characterized high- and low-voltage activated (HVA and LVA) calcium currents from hippocampal neurons at 4-10 days in vitro (DIV) obtained from wild-type (WT) and KLHL1-knockout mice (KLHL1 KO). HVA current density at +10 mV increased with time of culture in WT neurons, increasing by 40% from 7-10 (n=8) DIV compared to 4-6 DIV (n=14, Student?s T-test p0.05). KO mice displayed significantly decreased HVA current density (by 30%) at 4-6 DIV (n= 24, p0.0.5), suggesting that the deficit in HVA calcium current in the KOs was compensated for after 7 days in culture. Pharmacological dissection of HVA currents is being performed to determine the status of each individual current component. No differences in LVA current density were observed between WT and KO-KLHL1 neurons at any time point (n=24, p>0.0.5); interestingly, changes in the LVA current kinetics suggest that alpha 1I currents appears to compensate for a possible down-regulation of alpha1H at 7-10 DIV. Overall these results suggest HVA and LVA current components are altered in KLHL1 KO and that these deficits are compensated for in the KO neurons with different time courses in vitro.