[Background]
Monensin (Mo) has been reported to decrease the ATP content in various cells, however, its mechanisms are not fully understood in cardiac myocytes. In this study, the effects of Mo on ATP production was examined in guinea-pig ventricular myocytes.
[Methods]
The ATP production was evaluated from the time taken to open sarcolemmal K_ATP channel. Membrane potential and Ca²⁺ concentration of mitochondria (mito) was measured.
[Results]
When the extracellular solution containing 112 mM Na,o and the intracellular solution containing 10 mM Na,i and 0 mM ATP were used, Mo 10^-5 M shortened time taken to open the K_ATP channel significantly. When 0 mM Na,o and 10 mM Na,i were used, Mo also shortened time. Next, when 0 mM Na,o and 0 mM Na,i were used, Mo shortened the time to a lesser extent. When EGTA 5 mM was replaced by BAPTA 40 mM in the patch pipette, the time taken to open the K_ATP channel was not shortened so much by Mo. Mo increased mito Ca²⁺ and depolarized the membrane potential in saponin-treated myocytes.
[Conclusion]
We conclude that the Mo-induced Na⁺ influx into mito alters Na⁺/ Ca²⁺ exchange function, and the mito membrane depolarization may cause Ca²⁺ influx to mito matrix, leading to suppression of ATP production.