Is the mitochondrial Ca2+ uniporter a voltage‐modulated transport pathway?

The influence of membrane potential (delta psi) on Ca2+ transport through the Ca2+ uniporter (UP) was investigated in fura-2-loaded rat heart mitochondria at physiologically relevant-submicromolar-external [Ca2+]. In the absence of delta psi the UP could not mediate Ca2+ uptake even when an 8-fold external (approximately 500 nM) to internal (approximately 60 nM) [Ca2+] gradient was present and charge compensation was provided by acetate and the protonophore, CCCP. A small (approximately -120 mV) and transient delta psi (generated by valinomycin) resulted in a rise in matrix [Ca2+] only when external [Ca2+] exceeded 150 nM. At physiologically high (approximately -180 mV) and stable delta psi this threshold value for Ca2+ uptake dropped to 15 nM. The results indicate that (1) at physiological [Ca2+]o, delta psi in addition to being a component of delta mu Ca2+ seems to be necessary for providing a transport-competent conformation for the UP; and (2) below a threshold [Ca2+]o the UP cannot operate even in the presence of a high electric driving force.