TRPM8 Channels and SOCE: Modulatory Crosstalk between Na+ and Ca2+ Signaling

The electrochemical driving forces across the plasma membrane mediated by ion channels, pumps, and exchangers are essential for cellular homeostasis, regulating a wide range of biological processes [1,2]. Although both excitable (e.g., neurons) and non-excitable (e.g., lymphocytes) cells manage their cellular functions through plasmalemmal ion flux, excitable cells change the membrane potential mediated by depolarization and voltage-gated ion channels, while nonexcitable cells control this process by the different downstream processes and ligand-gated ion channels [2,3]. Sodium (Na+) is the principal extracellular cation, being carried to the intracellular space mainly through inward Na+ currents (INa) [2]. Pioneering studies documented that inhibition of INa, but not the calcium (Ca2+) absence, abolished the action potential, indicating that Na+ influx is essential for cell excitability, action Abstract