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

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Abstract
The influence of membrane potential (Δψ) 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 Δψ the UP could not mediate Ca2+ uptake even when an 8‐fold external (∼500 nM) to internal (∼60 nM) [Ca2+] gradient was present and charge compensation was provided by acetate and the protonophore, CCCP. A small (∼−120 mV) and transient Δψ (generated by valinomycin) resulted in a rise in matrix [Ca2+] only when external [Ca2+] exceeded 150 nM. At physiologically high (∼−180 mV) and stable Δψ this threshold value for Ca2+ uptake dropped to 15 nM. The results indicate that (1) at physiological [Ca2+]m Δψ in addition to being a component of ΔμCa2+ seems to be necessary for providing a transport‐competent conformation for the UP; and (2) below a threshold [Ca2+]m the UP cannot operate even in the presence of a high electric driving force.