Voltage-gated mobility of the Ca²⁺ channel cytoplasmic tails and its regulatory role

Transient increase in intracellular free Ca²⁺ concentration generated by the voltage-gated Ca_v1.2 channels acts as an important intracellular signal. By using fluorescence resonance energy transfer combined with patch clamp in living cells, we present evidence for voltage-gated mobility of the cytoplasmic tails of the Ca_v1.2 channel and for its regulatory role in intracellular signaling. Anchoring of the C-terminal tail to the plasma membrane caused an inhibition of its state-dependent mobility, channel inactivation, and CREB-dependent transcription. Release of the tail restored these functions suggesting a direct role for voltage-gated mobility of the C-terminal tail in Ca²⁺ signaling.