Calcium channels are establishing the link between calcium homeostasis and heart diseases.

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Calcium is one of the most important second messenger molecules used by living cells. Signaling carried out by calcium ions plays an important role in many cellular processes and because of its universal nature, disruption of calcium homeostasis under pathological conditions can have numerous consequences. Calcium homeostasis refers to the regulation of the concentration of calcium ions in the extracellular fluid [Ca++]ECF. 1. Calcium homeostasis is regulated by three hormones, parathyroid hormone, vitamin D and calcitonin[1]. 2. The calcium-sensing receptor (CASR) plays an important role in regulation of extracellular calcium[2]. 3. Additionally calcium homeostasis is tightly controlled because the calcium ions have a stabilizing effect on voltage-gated ion channels (VGCC). Calcium entry through VGCC is an important physiological event, and proper functioning of these channels is crucial in many cellular processes. VGCC are expressed in many diverse cells of the human body and their pharmacological properties are independent of the cell type where they reside. ? For instance, when [Ca++]ECF is too low (hypocalcemia), voltage-gated ion channels start opening spontaneously, causing nerve and muscle cells to become hyperactive. The syndrome of involuntary muscle spasms due to low [Ca++]ECF is called hypocalcemic tetany [3]. ? Conversely, when [Ca++]ECF is too high (hypercalcemia), voltage-gated ion channels don't open as easily, and there is depressed nervous system function. Another problem of hypercalcemia is that calcium can combine with phosphate ions, forming deposits of calcium phosphate (stones) in blood vessels and in the kidneys[3]. 4. Secondly, the connection between calcium channels and cardiovascular disease is plausible. Calcium deposits are part of artery-clogging plaque. They also contribute to stiffening of the arteries and interfere with the action of heart valves. But whether there is a direct connection between the amount of calcium in the bloodstream (calcium supplements increase blood calcium levels) and cardiovascular problems isn't yet known. 5. However the link between cardiac contractile dysfunction in patients with end-stage heart failure and aberrant myocardial intracellular calcium handling is now well established. A number of distinct sarcolemmal (L-type, N-type, T-type, P-type, Q-type) and sarcoplasmic reticular (calcium release, ryanodine) calcium channels that have been defined on a biophysical, biochemical, and molecular basis lend valuable insights into possible factors that may contribute to the abnormal calcium handling in the hearts of these patients[4]. What is now clear is that cardiac muscle contraction is a rigorously regulated event that follows the organized cycling of calcium from the sarcoplasmic reticulum (SR) into the cytosol and back into the SR, and that this cycle follows the graded entry of trigger calcium that enters the cell through the voltage-sensitive calcium channel. 1. Gregory R. Mundya and Theresa A. Guise Hormonal Control of Calcium Homeostasis , Clinical Chemistry. 1999;45:1347-1352. 2. Hendy GN, D'souza-Li L, Yang B, Canaff L, Cole D. Mutations of the calcium-sensing receptor (CASR) in familial hypocalciuric hypercalcaemia, neonatal severe hyperparathyroidism, and autosomal dominant hypocalcaemia. Human Mutation 2000;16:281-296. 3. E. A. Luk'yanets . International workshop on mechanisms of calcium homeostasis in excitable cells , Biomedical and Life Sciences Neurophysiology Volume 25, Number 6, 390-392, DOI: 10.1007/BF01053217 . 4. Peter J. Gengo, Physiologic and emerging pathophysiologic role of cardiac calcium channels , Heart Failure Reviews , Volume 1, Number 2, 151-164, DOI: 10.1007/BF00126379

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Author: Kirti V. Patel

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