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.
Kapùs
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A
Department of Physiology, Semmelweis University of Medicine, Budapest, Hungary.
Szászi
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K
Káldi
K
K
Ligeti
E
E
Fonyó
A
A
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D015759:Ionomycin / Q000494:pharmacology; D008564:Membrane Potentials; D008929:Mitochondria, Heart / Q000378:metabolism*; D011487:Protein Conformation; D051381:Rats; D014634:Valinomycin / Q000494:pharmacology
D015220:Calcium Channels; D002135:Calcium-Binding Proteins; C034703:mitochondrial calcium uniporter; D014634:Valinomycin; D015759:Ionomycin; D002118:Calcium