Calcium signalling in streptozotocin-induced type 1 diabetic rat heart

Administration of streptozotocin (STZ) to rats causes selective necrosis of pancreatic insulin producing beta-cells. In addition to hypoinsulinaemia, other characteristics of STZ-induced diabetic rat include hyperglycaemia, glucosuria, polydipsia, polyphagia, loss of body weight, hypercholesterolaemia and hypertriglyceridaemia. A variety of contractile defects have been frequently reported in various cardiac muscle preparations from STZ-treated rat. In ventricular myocytes defects include alterations to the time course and amplitude of contraction. During the process of excitation-contraction (E-C), coupling depolarisation of the ventricular myocyte membrane by an action potential opens voltage-gated L-type Ca²⁺ channels permitting a small influx of Ca²⁺ which triggers a large release of Ca²⁺ from the sarcoplasmic reticulum (SR) and a transient rise of intracellular Ca²⁺ concentration ([Ca²⁺]_i). Binding of Ca²⁺ to troponin C initiates the process of contraction. During relaxation of heart contraction cytosolic Ca²⁺ is transported back into the SR and effluxed from the cell primarily via the Na⁺/Ca²⁺ exchange. This review is concerned with the defects in Ca²⁺ signalling that underlie contractile dysfunction in STZ-induced diabetic rat heart.