Ca Signaling in Striated Muscle Cells During Intracellular Acidosis.

The cytosolic pH (pH) of mammalian cells is tightly maintained at values ~7.2. Cytoplasmic acidosis (pH < 6.8) occurs when the intracellular proton concentration ([H]) exceeds the buffering capacity of the cytosol and transport processes to extrude protons are exhausted. During intracellular acidosis, the contractility of cardiac and skeletal muscle cells is strongly reduced, often at sufficient Ca levels. A contraction of striated muscle is achieved when the intracellular calcium (Ca) concentration rises above resting levels. The amplitude and kinetics of Ca signals are controlled by Ca handling proteins and force is generated if Ca ions interact with contractile filaments of the sarcomere. Some aspects of this phenomenon, such as the biochemical origin of excessive protons in working muscle cells and molecular interactions of protons with Ca handling proteins or contractile filaments, are not yet fully understood. This review summarizes our current understanding of how striated muscle cells handle Ca and H and how a rise in [H] may interfere with Ca signaling in the working skeletal muscle (fatigue) or during ischemic events in cardiac muscle. Finally, we briefly address experimental strategies to measure Ca signaling at different pH values with fluorescent probes and highlight their limitations.