Carnosine: a novel peptide regulator of intracellular calcium and contractility in cardiac muscle

Abstract

Myocardial contractile failure is a common cause of morbidity and mortality in patients with ischemic heart disease and inflammatory disorders such as sepsis. Recent research indicates that contractile failure is associated with dysregulation of cytoplasmic calcium levels in the myocyte. However, the specific biochemical alterations responsible for calcium dysregulation remain unclear. In a search for mechanisms which might explain the altered calcium regulation in cardiac cells during ischemia and sepsis, we discovered new roles for an intracellular peptide which regulates intracellular calcium and contractility in myocardial cells. The intracellular peptide carnosine improves contraction in the isolated rat heart and increases free intracellular calcium levels. It stimulates calcium release from the ryanodine calcium-release channel, inhibits calcium uptake by the sarcoplasmic reticulum calcium pump, and sensitizes the contractile proteins to calcium. We believe that this peptide represents a new intracellular messenger system for the regulation/modulation of intracellular calcium. Changes in levels of carnosine may play a role in the altered contractility seen during critical illness.