期刊
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
卷 286, 期 3, 页码 H1124-H1132出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpheart.00162.2003
关键词
heart; store operated channels
资金
- NHLBI NIH HHS [T32 HL-07918] Funding Source: Medline
- NIDDK NIH HHS [DK-55647] Funding Source: Medline
Capacitative Ca2+ entry (CCE) refers to the influx of Ca2+ through plasma membrane channels activated on depletion of endoplasmic-sarcoplasmic reticulum Ca2+ stores. We utilized two Ca2+-sensitive dyes (one monitoring cytoplasmic free Ca2+ and the other free Ca2+ within the sarcoplasmic reticulum) to determine whether adult rat ventricular myocytes exhibit CCE. Treatments with inhibitors of the sarcoplasmic endoplasmic reticulum Ca2+-ATPases were not efficient in releasing Ca2+ from stores. However, when these inhibitors were coupled with either Ca2+ ionophores or angiotensin II (an agonist generating inositol 1,4,5 trisphosphate), depletion of stores was observed. This depletion was accompanied by a significant influx of extracellular Ca2+ characteristic of CCE. CCE was also observed when stores were depleted with caffeine. This influx of Ca2+ was sensitive to four inhibitors of CCE (glucosamine, lanthanum, gadolinium, and SKF-96365) but not to inhibitors of L-type channels or the Na+/Ca2+ exchanger. In the whole cell configuration, an inward current of similar to0.7 pA/pF at -90 mV was activated when a Ca2+ chelator or inositol (1,4,5)-trisphosphate was included in the pipette or when Ca2+ stores were depleted with a Ca2+-ATPase inhibitor and ionophore. The current was maximal at hyperpolarizing voltages and inwardly rectified. The channel was relatively permeant to Ca2+ and Ba2+ but only poorly to Mg2+ or Mn2+. Taken together, these data support the existence of CCE in adult cardiomyocytes, a finding with likely implications to physiological responses to phospholipase C-generating agonists.
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