Plasma Membrane Ca2+ Release-Activated Ca2+ Channels With A High Selectivity for Ca2+ Identified by Patch–Clamp Recording in Rat Liver Cells

Abstract

Repetitive waves of increased cytoplasmic Ca 2؉ concentration play a central role in the process by which hormones regulate liver function. Maintenance of these Ca 2؉ waves requires Ca 2؉ inflow through store-operated Ca 2؉ channels. The properties and mechanism(s) of activation of these channels are not well understood. Store-operated Ca 2؉ channels (SOCs) in the H4-IIE rat liver cell line were studied by whole-cell patch clamping. Increases in the concentration of Ca 2ϩ in the cytoplasmic space ([Ca 2ϩ ] cyt ) of hepatocytes play a central role in the mechanisms by which hormones and growth factors regulate intermediary metabolism, drug metabolism, the transport of bile acids and inorganic ions, and cell growth and differentiation. [1][2][3][4] One of the main types of intracellular Ca 2ϩ signals in hepatocytes is composed of repetitive waves of increased [Ca 2ϩ ] cyt that move within the cytoplasmic space of individual hepatocytes and from one hepatocyte to another along liver cell cords. 1,3-6 Within individual hepatocytes, it is often observed that the wave of increased [Ca 2ϩ ] cyt moves from the canalicular side to the basal side of the cell. 5 These Ca 2ϩ waves are initiated by the release of Ca 2ϩ from the endoplasmic reticulum induced by inositol 1,4,5-trisphosphate (InsP 3 ), and are propagated by InsP 3 -and Ca 2ϩ -induced Ca 2ϩ release from the endoplasmic reticulum through InsP 3 and ryanodine receptors, respectively.

Extracellular Zinc and ATP Restore Chloride Secretion across Cystic Fibrosis Airway Epithelia by Triggering Calcium Entry

“…Store-operated Ca 2ϩ channels play an important role in Ca 2ϩ entry in non-excitable cells (23,24) and in epithelial cells (25)(26)(27). Although zinc has been described as an inhibitor of store-operated Ca 2ϩ channels (23)(24)(25)(26)(27) Ϫ transport in IB3-1 CF cells grown on collagen-coated glass coverslips, we assessed Cl Ϫ efflux using 6-methoxy-N-(3-sulfopropyl)quinolinium halide fluorescence assay. ZnCl 2 (20 M) alone or in combination with ATP (100 M) stimulated Cl Ϫ efflux when administered in Na ϩ -free alkaline (pH 7.9) medium (Fig.…”

Hydrogen peroxide mobilizes Ca2+ through two distinct mechanisms in rat hepatocytes

“…Various hormones, including hepatocyte growth factor [31] , vasopressin [32] , insulin [33] , and norepinephrine [10] , have been reported to activate Ca 2+ -permeable channels. In addition, hepatocytes possess Ca 2+ release-activated Ca 2+ channels [4,34,35] . Membrane currents through Ca 2+ releaseactivated Ca 2+ channels (I CRAC ) can be recorded in intact hepatocytes [35] , and both ATP and vasopressin can activate I CRAC [36] , suggesting that this type of channel is capable of being opened without altering the volume of Ca 2+ stores.…”

“…The development of ischemia-reperfusion injury is a major risk factor associated with liver transplantation [1][2][3][4] and coronary bypass surgery [5] . In the liver, one of the mechanisms causing ischemia-reperfusion injury seems to be oxidative stress to liver cells (hepatocytes), which occurs when pro-oxidants overwhelm cellular anti-oxidant defense mechanisms [3,6] .…”

A Case of Iron Overload Cardiomyopathy Beneficial Effects of Iron Chelating Agent and Calcium Channel Blocker on Left Ventricular Dysfunction

“…Oudit, et al suggested that calcium channel blockers may exert much more beneficial effects on cardiomyocytes and endocrine cells, 3) which express higher levels of L-type Ca 2+ channels than hepatocytes. 3,10,11) However, impaired glucose tolerance in this case had progressed to diabetes mellitus, although the iron chelating agent and the calcium channel blocker improved LV dysfunction. This endocrine disorder may not be attributable mainly to iron overload.…”