Mechanisms of hemolysate-induced [Ca2+](i) elevation in cerebral smooth muscle cells

H. Zhang*, B. Weir, L. S. Marton, R. L. Macdonald, V. Bindokas, R. J. Miller, J. R. Brorson

*Corresponding author for this work

Research output: Contribution to journalArticle

67 Scopus citations

Abstract

The effects of hemolysate on free cytosolic [Ca2+] ([Ca2+](i)) homeostasis were studied in freshly isolated rat basilar artery smooth muscle cells using fura 2 and dual excitation wave-length microfluorimetry. Hemolysate reversibly produced a transient [Ca2+](i) peak followed by a slowly decaying plateau which was absent in Ca2+-free solution. This effect of hemolysate was attenuated by 1) the sarcoplasmic reticulum Ca2+ pump inhibitors thapsigargin and cyclopiazonic acid, 2) the Ca2+ release- blocking agents ryanodine and dantrolene, 3) the cytochrome P-450 inhibitor econazole, and 4) the inorganic Ca2+ channel blocker lanthanum but was not significantly attenuated by 1) the receptor-regulated Ca2+ channel blocker SKF-96365 or 2) the voltage-dependent Ca2+ channel blocker nimodipine. Fractionation of hemolysate using membranes with specific pore sizes (0.5, 1, and 12-14 kDa) indicated that a component(s) >0.5 but <1 kDa could produce a similar [Ca2+](i) peak and plateau while fractions > 1 and > 12-14 kDa produced a small and slow [Ca2+](i) rise without a significant peak. ATP, which was found in hemolysate, produced a [Ca2+](i) response similar to that of hemolysate. P2-purinoceptor antagonists significantly attenuated the effect of ATP, hemolysate, and the fractions < 1 and < 12-14 kDa. We conclude that hemolysate elevates [Ca2+](i) by both releasing Ca2+ from internal stores and triggering Ca2+ entry, possibly from a voltage-independent Ca2+ influx pathway, an effect apparently identical to that of ATP.

Original languageEnglish (US)
Pages (from-to)H1874-H1890
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume269
Issue number6 38-6
DOIs
StatePublished - 1995

Keywords

  • adenosine 5'-triphosphate
  • cerebrovascular smooth muscle cells

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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