PIP2 hydrolysis is responsible for voltage independent inhibition of CaV2.2 channels in sympathetic neurons
2013
Vivas, Oscar | Castro, Hector | Arenas, Isabel | Elías-Viñas, David | García, David E.
GPCRs regulate CaV2.2 channels through both voltage dependent and independent inhibition pathways. The aim of the present work was to assess the phosphatidylinositol-4,5-bisphosphate (PIP2) as the molecule underlying the voltage independent inhibition of CaV2.2 channels in SCG neurons. We used a double pulse protocol to study the voltage independent inhibition and changed the PIP2 concentration by means of blocking the enzyme PLC, filling the cell with a PIP2 analogue and preventing the PIP2 resynthesis with wortmannin. We found that voltage independent inhibition requires the activation of PLC and can be hampered by internal dialysis of exogenous PIP2. In addition, the recovery from voltage independent inhibition is blocked by inhibition of the enzymes involved in the resynthesis of PIP2. These results support that the hydrolysis of PIP2 is responsible for the voltage independent inhibition of CaV2.2 channels.
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