Rat arterial smooth muscle devoid of ryanodine receptor function: effects on cellular Ca<sup>2+</sup> handling

British Journal of Pharmacology - Tập 132 Số 8 - Trang 1957-1966 - 2001
Karl Dreja1, Ina Nordström1, Per Hellstrand1
1Department of Physiological Sciences, Lund University, Lund, Sweden

Tóm tắt

The roles of intracellular Ca2+ stores and ryanodine (Ry) receptors for vascular Ca2+ homeostasis and viability were investigated in rat tail arterial segments kept in organ culture with Ry (10 – 100 μM) for up to 4 days. Acute exposure to Ry or the non‐deactivating ryanodine analogue C10‐Oeq glycyl ryanodine (10 μM) eliminated Ca2+ release responses to caffeine (20 mM) and noradrenaline (NA, 10 μM), whereas responses to NA, but not caffeine, gradually returned to normal within 4 days of exposure to Ry. Ry receptor protein was detected on Western blots in arteries cultured either with or without Ry. Brief Ca2+ release events (sparks) were absent after culture with Ry, whereas Ca2+ waves still occurred. The propagation velocity of waves was equal (∼19 μm s−1) in tissue cultured either with or without Ry. Inhibition of Ca2+ accumulation into the sarcoplasmic reticulum (SR) by culture with caffeine (5 mM), cyclopiazonic acid or thapsigargin (both 10 μM) decreased contractility due to Ca2+‐induced cell damage. In contrast, culture with Ry did not affect contractility. Removal of Ca2+ from the cytosol following a Ca2+ load was retarded after Ry culture. Thapsigargin reduced the rate of Ca2+ removal in control cultured rings, but had no effect after Ry culture. It is concluded that intracellular Ca2+ stores recover during chronic Ry treatment, while Ry receptors remain non‐functional. Ry receptor activity is required for Ca2+ sparks and for SR‐dependent recovery from a Ca2+ load, but not for Ca2+ waves or basal Ca2+ homeostasis. British Journal of Pharmacology (2001) 132, 1957–1966; doi:10.1038/sj.bjp.0703986

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British Journal of Pharmacology

Tập 132 Số 8

1957-1966

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