PIP2 hydrolysis is responsible for voltage independent inhibition of CaV2.2 channels in sympathetic neurons

► We used patch-clamping to study voltage-independent inhibition of CaV2.2 channels. ► We changed PIP2 concentration by internal dialysis and a voltage-sensitive phosphatase (VSP). ► Voltage-independent inhibition requires PLC and it is prevented by exogenous PIP2. ► Voltage-independent inhibition is sensitive to enzymes affecting PIP2 resynthesis. ► PIP2 hydrolysis accounts to the voltage-independent inhibition of CaV2.2 channels.