Levosimendan is a mitochondrial K(ATP) channel opener

Area of Science:

• Biochemistry
• Cardiovascular Pharmacology

Background:

• Levosimendan is an inodilator used for heart failure.
• It is known to cause vasodilation by opening plasma membrane KATP channels in vascular smooth muscle cells.

Purpose of the Study:

• To investigate the effects of levosimendan on mitochondrial KATP channels.
• To determine if levosimendan affects mitochondrial function.

Main Methods:

• Developed a sensitive method using rat liver mitochondria to assess KATP channel activity.
• Measured mitochondrial transmembrane potential (DeltaPsi) and respiration rates.
• Tested levosimendan's effects in varying potassium concentrations and with a selective mitochondrial KATP channel blocker (5-hydroxydecanoate).

Main Results:

• Levosimendan (0.7-2.6 microM) decreased mitochondrial DeltaPsi (6.5-40.4%) in a K+-dependent manner.
• This effect was abolished by 5-hydroxydecanoate, confirming mitochondrial KATP channel involvement.
• Levosimendan did not affect mitochondrial respiration or transmembrane potential at tested concentrations.

Conclusions:

• Levosimendan actively opens mitochondrial KATP channels.
• This finding suggests a novel mechanism of action for levosimendan beyond plasma membrane effects.