Rat arterial smooth muscle devoid of ryanodine receptor function: effects on cellular Ca2+ handling

• 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 M) for up to 4 days. Acute exposure to Ry or the non-deactivating ryanodine analogue C10-Oeq glycyl ryanodine (10 M) eliminated Ca2+ release responses to caffeine (20 mM) and noradrenaline (NA, 10 M), 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 m 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 M) 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Nyckelord

Ryanodine receptors

smooth muscle

Ca2+ stores

sarcoplasmic reticulum

organ culture

Ca2+ sparks

Ca2+ waves

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art (ämneskategori)

ref (ämneskategori)