Sympathetic Voltage-Independent Regulation of Voltage- Gated Calcium Channels in Pancreatic β-Cells
Journal Title: Journal of Endocrinology and Diabetes - Year 2018, Vol 5, Issue 1
Abstract
Voltage-gated calcium (CaV) channels are regulated by G proteins via voltage-dependent and independent pathways. Voltage-independent regulation of calcium channels is important for intracellular calcium concentration and insulin secretion. Voltage dependence of each pathway can be elucidated by a prepulse facilitation protocol. Using this experimental approach, we compared CaV regulation by GTPγS and noradrenaline (NA) in rat pancreatic β-cells and rat superior cervical ganglion (SCG) neurons. The SCG neuron is a model in which the bases of CaV channel regulation by G proteins have been established. CaV channel regulation through activation of the sympathetic nervous system has been poorly studied in native insulin-secreting cells. We recorded CaV channel currents by means of the patch-clamp technique in the whole-cell configuration. We found that application of both GTPγS (a nonspecific activator of G proteins) by cell dialysis and noradrenaline (NA)-exposure reduced CaV current amplitude in pancreatic β-cells and in SCG neurons. However, the inhibition of CaV channel currents in GTPγS-dialyzed SCG neurons was relieved by a strong depolarizing pulse. By contrast, in pancreatic β-cells, the inhibition was maintained after a strong depolarizing pulse. In SCG neurons, the CaV channel inhibition by NA is predominantly voltage-dependent, whereas in pancreatic β-cells it is only 40%. Thus, it appears that CaV channels in rat pancreatic β-cells are regulated mainly through a voltage-independent pathway. The signaling pathway for CaV channel regulation by NA in pancreatic β-cells appears to differ from the classic signaling pathway described in SCG neurons. Therefore, voltage-independent regulation of Ca2+ entry through CaV channels is a critical step in understanding the pathophysiology of type 2 diabetes.
Authors and Affiliations
David E. Garcia, Lizbeth de la Cruz, Arturo Reyes-Vaca, Julieta Garduño, Isabel Arenas
Keywords
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- EP ID EP334045
- DOI 10.15226/2374-6890/5/1/00194
- Views 110
- Downloads 0
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