January 1, 2015Open Access
Ca2+-Activated K+ Channels as Therapeutic Targets for Myocardial and Vascular Protection
Key Result
Modulation of large- and small-conductance Ca2+-activated K+ channels (BKCa and SKCa) offers potential therapeutic benefits for cardioprotection against ischemic injury, arrhythmia, and heart failure.
Structured PICO
P
Population
Cardiomyocytes and vascular smooth muscle cells (preclinical/basic science context)
I
Intervention
Modulation/activation of small- and large-conductance Ca(2+)-activated K(+) channels (SKCa and BKCa)
O
Outcome
Cardioprotection (improved function, reduced infarct size, vasodilation)
Modulation of cardiomyocyte and endothelial SKCa and BKCa channels represents a promising therapeutic target for cardioprotection against ischemic injury, heart failure, and arrhythmias.
Limitations
- Lack of highly specific and potent pharmacological tools for BKCa and SKCa channels.
- Current pharmacological agents have significant off-target effects.
Abstract
Small- and large-conductance Ca(2+)-activated K(+)channels (SKCa and BKCa, respectively) may be important targets for therapeutic interventions in a variety of cardiac conditions. In cardiomyocytes, BKCa channels are localized to mitochondria where they beneficially modulate reactive oxygen species, mitochondrial Ca(2+), and respiration. In vascular smooth muscle cells, BKCa channels regulate vascular tone and promote vasodilation. Activation of BKCa channels has demonstrated significant cardioprotection following ischemic injury, including improved function and reduced infarct size. SKCa channels are expressed in both the membrane and mitochondria of cardiomyocytes. Modulation of cardiomyocyte SKCa channels may be beneficial for arrhythmia, heart failure, and ischemia. Mitochondrial SKCa channels may provide similar benefit to BKCa channels. In addition, activation of SKCa channels on the endothelium promotes vasodilation. This mini-review focuses on the modulation of cardiomyocyte BKCa and SKCa channels for cardioprotection and briefly address associated potential therapeutic benefits in the coronary circulation.