Mitochondrial Ca2+ uptake is important over low [Ca2+]i range in arterial smooth muscle

MitochondriaI Ca2+ uptake is usually thought to occur only when intracellular Ca2+ concentration ([Ca2+](i)) is high. We investigated whether mitochondrial Ca2+ removal participates in shaping [Ca2+](i) signals in arterial smooth muscle over a low [Ca2+](i) range. [Ca2+](i) was measured using fura 2-loaded, voltage-clamped cells from rat femoral arteries. Both diazoxide and carbonyl cyanide m-chlorophenylhydrazone (CCCP) depolarized the mitochondria. Diazoxide application increased resting [Ca2+](i), suggesting that Ca2+ is sequestered in mitochondria. Over a low [Ca2+](i) range, diazoxide and CCCP slowed Ca2+ removal rate, determined after a brief depolarization. When [Ca2+](i) was measured during sustained depolarization to -30 mV, CCCP application increased [Ca2+](i). When Ca2+ transients were repeatedly evoked by caffeine applications, CCCP application elevated resting [Ca2+](i). Caffeine-induced Ca2+ transients were compared before and after CCCP application using the half decay time, or time required to reduce increase in [Ca2+](i) by 50% (t(1/2)). CCCP treatment significantly increased t(1/2) These results suggest that Ca2+ removal to mitochondria in arterial smooth muscle cells may be important at a low [Ca2+](i).