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


RESULTS
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).


CONCLUSIONS
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.
Department of Physiology, College of Medicine & Health Sciences, UAE University, Al Ain, UAE.
Zannatul
Z
Ferdous
Department of Physiology, College of Medicine & Health Sciences, UAE University, Al Ain, UAE.
Muhammad Anwar
MA
Qureshi
Department of Physiology, College of Medicine & Health Sciences, UAE University, Al Ain, UAE.
Petrilla
P
Jayaprakash
Department of Physiology, College of Medicine & Health Sciences, UAE University, Al Ain, UAE.
Khatija
K
Parekh
Department of Biochemistry, College of Medicine & Health Sciences, UAE University, Al Ain, UAE.
Annie
A
John
Department of Pharmacology, College of Medicine & Health Sciences, UAE University, Al AIn, UAE.
Murat
M
Oz
Department of Biochemistry, College of Medicine & Health Sciences, UAE University, Al Ain, UAE.
Haider
H
Raza
Institute of Cardiovascular Sciences, University of Manchester, Manchester, United Kingdom.
Halina
H
Dobrzynski
Department of Physiology, College of Medicine & Health Sciences, UAE University, Al Ain, UAE.
Thomas Edward
TE
Adrian
Department of Physiology, College of Medicine & Health Sciences, UAE University, Al Ain, UAE.
Frank Christopher
FC
Howarth
D000200:Action Potentials; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000503:physiopathology*; D006339:Heart Rate; D008297:Male; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D012849:Sinoatrial Node / Q000378:metabolism / Q000503:physiopathology*; D059467:Transcriptome
D012333:RNA, Messenger