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
Related Articles
- EP ID EP334045
- DOI 10.15226/2374-6890/5/1/00194
- Views 113
- Downloads 0
Polycystic Ovary Syndrome: Explaining the Gynecological Aspects and Treatment Options to Patients
Polycystic Ovary Syndrome (PCOS) is one of the most prevalent conditions leading to reproductive and metabolic health concerns for women. The apparently disparate consequences of this disorder ranging from menstrual dysf...
Hypercalcemia following Alfacalcidol for Post-Surgical Hypoparathyroidism-An Underestimated Complication?
Background: Post operative hypocalcemia is a common complication of thyroid and parathyroid surgery and is treated with calcium and/or active Vitamin D supplements, such as alfacalcidol. Although reportedly uncommon, we...
Maternal Diabetes Mellitus – Risk Factor for Fetus and Infant
Diabetes during pregnancy may occur as pregestational or gestational diabetes mellitus. Throughout gestation there is a close relationship between maternal and fetal blood glucose concentrations. Maternal hyperglycemia l...
Parathyroid Gland FNA and PTH Washout; Diagnostic Value in Patients with Primary Hyperparathyroidism
Primary hyperparathyroidism is the most common cause of hypercalcemia in outpatients and it is usually attributed to parathyroid adenoma, which is managed by surgical resection of the adenoma. Successful management requi...
Favorable Effect of Bromocriptine and Pentoxifylline in Mild Graves Disease Orbitopathy: A Randomized, Open, Clinical Trial
Background:Graves’ orbitopathy (GO) is the most frequent extra thyroidal manifestation of Graves’ disease. Treatment for mild cases consists in euthyroidism restoration and topical treatments. Aim: To evaluate the effec...