Calcium influx at hyperpolarized membrane potentials modulates depolarization‐triggered exocytosis in bovine chromaffin cells.

Perturbations in Ca 2+ entry via neuronal transient receptor potential (TRP) and ORAI family proteins have been shown to alter synaptic transmission, and suggested to play a role in several neurodegenerative diseases including Huntington's, Alzheimer's and Parkinson's diseases. Specific mechanisms by which of TRP/ORAI channels modulate synaptic signaling are not completely understood. To determine the role of Ca 2+ influx trough non‐voltage gated Ca 2+ channels in regulation of neurotransmitter release, we investigated effects of modulation of Ca 2+ influx at hyperpolarized voltages on exocytosis in bovine chromaffin cells using a combination of imaging and electrophysiological techniques. We found that a small inwardly directed membrane current whose amplitude was dependent on the concentration of extracellular Ca 2+ and Na + , was present at resting membrane potential. Augmentation of this current either by hyperpolarization (from −50 mV to −90 mV) or stimulation with bradykinin (1 μM), a catecholamine secretagogue, elevated cytosolic Ca 2+ concentration at hyperpolarized potentials and facilitated exocytotic responses triggered by short depolarizations (<500 ms in duration). Exocytotic responses triggered by long depolarizations (>500 ms in duration) were suppressed at hyperpolarized holding potentials. Reversal of Na + /Ca 2+ exchanger by removal of Na + from bath solution did not cause depolarization‐independent exocytosis at −50 mV holding potential. Membrane hyperpolarization from −50 mV to −90 mV in the absence of direct Na + /Ca 2+ exchanger activity evoked depolarization‐independent exocytosis. Our findings provide first experimental evidence that in neuroendocrine cells perturbation in Ca 2+ influx at negative voltages with physiologically relevant stimuli significantly modulates exocytotic responses to depolarization‐triggered Ca 2+ entry via voltage‐gated Ca 2+ channels, and that Ca 2+ influx via native Ca 2+ channels operating at negative voltages is functionally coupled with Na + /Ca 2+ exchanger. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .