Different Profile of mRNA Expression in Sinoatrial Node from Streptozotocin-Induced Diabetic Rat

• Published in: PloS one 2016-04, Vol.11 (4), p.e0153934-e0153934
• Main Authors: Ferdous, Zannatul, Qureshi, Muhammad Anwar, Jayaprakash, Petrilla, Parekh, Khatija, John, Annie, Oz, Murat, Raza, Haider, Dobrzynski, Halina, Adrian, Thomas Edward, Howarth, Frank Christopher
• Format: Article
• Language: English
• Subjects: Action potential; Action Potentials; Animals; Biochemistry; Biology and Life Sciences; Calcium; Calcium (intracellular); Calcium transport; Cardiac arrhythmia; Cardiovascular disease; Cardiovascular diseases; Coding; Complications and side effects; Conduction; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - genetics; Diabetes Mellitus, Experimental - physiopathology; Gene expression; Genes; Genetic aspects; Glucose; Health sciences; Heart Rate; Intracellular; Male; Medicine; Medicine and Health Sciences; MicroRNA; Mortality; Peptides; Physical Sciences; Physiological aspects; Physiology; Polymerase chain reaction; Potassium; Potassium channels; Proteins; Rats; Rats, Wistar; Regulatory proteins; Reverse transcription; Risk factors; RNA, Messenger - genetics; Rodents; Ryanodine receptors; Sinoatrial Node - metabolism; Sinoatrial Node - physiopathology; Sodium; Streptozocin; Suction; Transcriptome; Transport
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0153934

Experiments in isolated perfused heart have shown that heart rate is lower and sinoatrial node (SAN) action potential duration is longer in streptozotocin (STZ)-induced diabetic rat compared to controls. In sino-atrial preparations the pacemaker cycle length and sino-atrial conduction time are prolonged in STZ heart. To further clarify the molecular basis of electrical disturbances in the diabetic heart the profile of mRNA encoding a wide variety of proteins associated with the generation and transmission of electrical activity has been evaluated in the SAN of STZ-induced diabetic rat heart. Heart rate was measured in isolated perfused heart with an extracellular suction electrode. Expression of mRNA encoding a variety of intercellular proteins, intracellular Ca2+-transport and regulatory proteins, cell membrane transport proteins and calcium, sodium and potassium channel proteins were measured in SAN and right atrial (RA) biopsies using real-time reverse transcription polymerase chain reaction techniques. Heart rate was lower in STZ (203±7 bpm) compared to control (239±11 bpm) rat. Among many differences in the profile of mRNA there are some worthy of particular emphasis. Expression of genes encoding some proteins were significantly downregulated in STZ-SAN: calcium channel, Cacng4 (7-fold); potassium channel, Kcnd2 whilst genes encoding some other proteins were significantly upregulated in STZ-SAN: gap junction, Gjc1; cell membrane transport, Slc8a1, Trpc1, Trpc6 (4-fold); intracellular Ca2+-transport, Ryr3; calcium channel Cacna1g, Cacna1h, Cacnb3; potassium channels, Kcnj5, Kcnk3 and natriuretic peptides, Nppa (5-fold) and Nppb (7-fold). Collectively, this study has demonstrated differences in the profile of mRNA encoding a variety of proteins that are associated with the generation, conduction and regulation of electrical signals in the SAN of STZ-induced diabetic rat heart. Data from this study will provide a basis for a substantial range of future studies to investigate whether these changes in mRNA translate into changes in electrophysiological function.