Ca2+-Independent But Voltage-Dependent Quantal Catecholamine Secretion (Civds) In Sympathetic Nervous System

Action potential induced vesicular exocytosis is considered exclusively Ca2+-dependent in Katz's Ca2+ hypothesis on synaptic transmission. This long-standing concept gets an exception following the discovery of Ca2+-independent but voltage-dependent secretion (CiVDS) and its molecular mechanisms in dorsal root ganglion sensory neurons. However, whether CiVDS presents only in sensory cells remains elusive. By combining multiple independent recordings, we find (1) CiVDS robustly presents in sympathetic nervous system, including sympathetic superior cervical ganglion (SCG) neurons and slice adrenal chromaffin cells, (2) uses voltage sensors of Ca2+ channels (N-type and novel L-type), and (3) contributes to catecholamine release in both homeostatic and fight-or-flight like states; (4) CiVDS-mediated catecholamine release is faster than that of Ca2+-dependent secretion at quantal level and (5) increases Ca2+ currents and contractility of cardiac myocytes. CiVDS presents in sympathetic nervous system with potential physiological functions including cardiac muscle contractility. In addition, there are evidences that CiVDS may present in other important types of cells. Supported by grants from NSFC, MOST and the CLS-program