Sodium-calcium exchanger and R-type Ca2+ channels mediate spontaneous [Ca2+]i oscillations in magnocellular neurones of the rat supraoptic nucleus. Issue 6 (June 2016)

• Record Type: Journal Article
• Authors: Kortus, Stepan; Srinivasan, Chinnapaiyan; Forostyak, Oksana; Zapotocky, Martin; Ueta, Yoichi; Sykova, Eva; Chvatal, Alexandr; Verkhratsky, Alexei; Dayanithi, Govindan
• Is Part Of: Cell calcium. Volume 59:Issue 6(2016)
• Page Start: 289
• Page End: 298
• Publication Date: 2016-06
• Subjects: AVP arginine vasopressin -- OT oxytocin -- SON supraoptic nucleus -- [Ca2+]i intracellular Ca2+ concentration -- SERCA sarcoendoplasmic reticulum Ca2+-ATPase -- VGCC voltage-gated Ca2+ channels -- EGTA ethylene glycol (bis-aminoethyl ether)-N, N, N′, N′-tetra acetic acid -- TTX tetrodotoxin -- PMCA plasmatic-Ca2+-ATPase -- CCCP carbonyl cyanide 3-chlorophenylhydrazone -- 4-AP 4-aminopirydine -- PACAP pituitary adenylate cyclase activating polypeptide -- NCX Na+/Ca2+ exchanger -- GABA gamma-aminobutyric acid -- AHP after hyperpolarisation -- DAP depolarizing after potential -- InsP3 1, 4, 5-trisphosphate -- DMSO dimethyl sulfoxide -- eGFP enhanced green fluorescent protein -- mRFP monomeric red fluorescent protein -- NMDG-Cl N-methyl-d-glutamine -- CPA cyclopiazonic acid -- ER endoplasmic reticulum; Ca2+ signalling -- Voltage-gated Ca2+ channels -- Ca2+ homeostasis -- Ca2+ imaging -- Ca2+ oscillations -- Ca2+ clearance -- Transgenic rats -- Vasopressin -- Oxytocin -- Hypothalamus -- Supraoptic nucleus -- Na+/Ca2+ exchanger -- Mitochondria -- Plasma membrane calcium pump -- Sarcoendoplasmic reticulum Ca2+-ATPase -- GABA -- Glutamate -- 1, 4, 5-Trisphosphate -- Tetrodotoxin -- Ca2+ channel toxins; Calcium -- Metabolism -- Periodicals; Vertebrates -- Physiology -- Periodicals; Calcium -- Physiological effect -- Periodicals; Cell physiology -- Periodicals; Calcium in the body -- Periodicals; 572.516
• DOI: 10.1016/j.ceca.2016.03.010
• Languages: English
• ISSNs: 0143-4160

Abstract

Graphical abstract: Schematic diagram shows the possible Ca 2+ transport mechanisms with highlights (red) of those that were identified as essential for [Ca 2+ ]i oscillations in the magnocellular neurones of the supraoptic nucleus. Highlights: Mechanisms of spontaneous [Ca 2+ ]i oscillations observed in the supraoptic nucleus vasopressin and oxytocin neurones have been found. Extracellular Ca 2+ is essential for oscillations whereas targeting intracellular Ca 2+ stores did not prevent cells from oscillations. Oscillations are mainly regulated by the high-voltage-dependent Ca 2+ channels dominated by R-type channel, the Na + /Ca 2+ exchanger in the reverse mode, and the plasmatic-Ca 2+ -ATPase pump. Oscillations may need changes in membrane potential but do not require action potentials. The mitochondrial role in the oscillations is less clear. Abstract: Isolated supraoptic neurones generate spontaneous [Ca 2+ ]i oscillations in isolated conditions. Here we report in depth analysis of the contribution of plasmalemmal ion channels (Ca 2+, Na + ), Na + /Ca 2+ exchanger (NCX), intracellular Ca 2+ release channels (InsP3 Rs and RyRs), Ca 2+ storage organelles, plasma membrane Ca 2+ pump and intracellular signal transduction cascades into spontaneous Ca 2+ activity. While removal of extracellular Ca 2+ or incubation with non-specific voltage-gated Ca 2+ channel (VGCC) blocker Cd 2+ suppressed the oscillations, neither Ni 2+ nor TTA-P2, the T-type VGCC blockers, had an effect. Inhibitors of VGCC nicardipine, ω-conotoxin GVIA, ω-conotoxin MVIIC, ω-agatoxin IVA (for L-, N-, P and P/Q-type channels, respectively) did not affect [Ca 2+ ]i oscillations. In contrast, a specific R-type VGCC blocker SNX-482 attenuated [Ca 2+ ]i oscillations. Incubation with TTX had no effect, whereas removal of the extracellular Na + or application of an inhibitor of the reverse operation mode of Na + /Ca 2+ exchanger KB-R7943 blocked the oscillations. The mitochondrial uncoupler CCCP irreversibly blocked spontaneous [Ca 2+ ]i activity. Exposure of neurones to Ca 2+ mobilisers (thapsigargin, cyclopiazonic acid, caffeine and ryanodine); 4-aminopyridine (A-type K + current blocker); phospholipase C and adenylyl cyclase pathways blockers U-73122, Rp-cAMP, SQ-22536 and H-89 had no effect. Oscillations were blocked by GABA, but not by glutamate, apamin or dynorphin. In conclusion, spontaneous oscillations in magnocellular neurones are mediated by a concerted action of R-type Ca 2+ channels and the NCX fluctuating between forward and reverse modes.