Cardiac Muscle Excitation Contraction Mediated From Sarcoplasmic Reticulum Biology Essay

Cardiac Muscle Excitation Contraction Mediated From Sarcoplasmic Reticulum Biology Essay In cardiac muscle, excitation-contraction coupling is mediated by calcium-induced calcium release from the sarcoplasmic reticulum through ryanodine receptors that are activated by calcium entry through L-type calcium channels on the sarcolemmal membrane. Although Ca2+ induced Ca2+ release triggered by the L-typed calcium current is the primary pathway for triggering Ca2+ from the sarcoplasmic reticulum, there are many other mechanisms that can also activate Ca2 + release from the sarcoplasmic reticulum such as Calcium induced calcium release (CICR) induced by T-typed calcium current, CICR triggered by calcium influx through Na+/Ca2+ exchange, and CICR mediated by calcium through tetrodotoxin (TTX)-sensitive Ca2+ current (ICa,TTX). As calcium is an important second messenger which is essential in regulating cardiac electrical activity as well as being the main activator of the myofilaments to which cause cardiac contraction. Mishandling of calcium is thought to lead many pathophysiol ogical conditions.  Knowledge of the mechanisms involved in regulating intracellular calcium and therefore contraction of the heart, may help to prevent and/or treat pathological conditions such as cardiac hypertrophy, arrhythmias or heart failure by using therapeutic agents targeted at modulating intracellular calcium. LIST OF FIGURES Figure 1: Calcium transport in ventricular myocytes 3 Figure 2: Six possible mechanism of cardiac excitation-contraction coupling 9 LIST OF ABBREVIATIONS LTCC = L-type calcium channels CICR = Calcium induced calcium release ECC = Excitation-contraction coupling NCX = Sodium-Calcium Exchange SR = Sarcoplasmic Recticulum ICa = Calcium current ICa,T = T-type calcium current ICa,L = L-type calcium current ICa,TTX = Tetrodotoxin-sensitive calcium current RyRs = Ryanodine Receptor [Ca2+]i = Intracellular calcium concentration [Ca2+]Tot = Total concentration of Calcium PKA = Protein Kinase A LVH = Left Ventricular Hypertrophy HOCM = Hypertrophic obstructiv e cardiomyopathy Introduction In heart muscle cell, the depolarization of action potential is due to the entering of Na+ ions via voltage gated Na+ channels and it is called fast inward current. The immediate repolarization is not possible due to rapidly inactivation of Na+ channel and initial depolarization allow the entering of calcium through voltage-grated Ca2+ channels and it is called second or the slow inward current. The rate of sodium channels inactivation is more rapid than that of calcium channels so that Ca2+ enters into the cell providing the membrane potential to close to 0mV for some part of action potential of heart muscle (Reuter, 1984). Excitation-contraction coupling (ECC) is the process in which an action potential triggers a myocyte to contract. In excitable muscle cells, the excitation signal causes rapid depolarization that produces the physiological response of contraction. Calcium is a ubiquitous second messenger, important in both, regulating the electrical activity of the heart as well as stimulating the myofilaments directly to cause contraction (Bers, 2001). In mammalian cardiac myocytes, the process of ECC is mediated by Ca2+ influx from the extracellular space that triggers Ca2+ Calcium – induced Calcium release (CICR) from the sarcoplasmic reticulum (SR) (Bers, 1991; Stern & Lakatta, 1992). When action potential reaches the myocyte, causing it to undergo depolarization, which causes calcium ions to enter the cell through L type calcium channel located on the sarcolemma and thereby trigger calcium release from the SR. Calcium influx and the intracellular calcium concentration trigger the contraction of heart due to binding of Ca2+ to cardiac muscle fiber protein, troponin C. For activation of SR calcium release, the L-type calcium current is the most widely accepted mechanism thought to be responsible for CICR. However, SR calcium release can also be triggered by calcium influx through sodium-calcium exchange, calcium infl ux via T-type Ca2+ current or through tetrodotoxin-sensitive Ca2+ current, or Inositol (1,4,5)-triphosphate (but not so much in cardiac muscle). Declining of calcium level in the cells cause the detachment of calcium from myofilament and resulting in relaxation of the heart. There are four main pathways for Ca2+ transport out of the cytosol including SR Ca2+ ATPase, sarcolemmal Ca2+-ATPase or mitochondrial Ca2+ uniport and sarcolemmal Na+/Ca2+ exchange. (Bers, 2002).