TY - JOUR
T1 - Halothane alters contractility and Ca2+ transport in ventricular myocytes from streptozotocin-induced diabetic rats
AU - Woodall, Alyson
AU - Bracken, Nicolas
AU - Qureshi, Anwar
AU - Howarth, Frank Christopher
AU - Singh, Jaipaul
N1 - Funding Information:
This work was supported by generous funding from the 401 British Heart Foundation and the British Council. The au-402 thors would also like to acknowledge the help of Dr. Simon 403 Harrison (Biomedical Sciences, University of Leeds) and Dr. 404 George Lees (Department of Pharmacology, University of 405 Sunderland) for their technical advice. We also thank Lisa 406 Whittaker for correcting the manuscript. 407
PY - 2004/6
Y1 - 2004/6
N2 - General anaesthetics have previously been shown to have profound effects on myocardial function. Moreover, many patients suffering from diabetes mellitus are anaesthetised during surgery. This study investigated compromised functioning of cardiac myocytes from streptozotocin (STZ)-induced diabetic rats and the additive effects of halothane on these dysfunctions. Ventricular myocytes were isolated from 8 to 12 weeks STZ-treated rats. Contraction and intracellular free calcium concentration ([Ca2+]i) were measured in electrically field-stimulated (1 Hz) fura-2-AM-loaded cells using a video-edge detection system and a fluorescence photometry system, respectively. L-type Ca2+ current was measured in whole cell, voltage-clamp mode. Halothane significantly (p<0.01) depressed the amplitude and the time course of the Ca2+ transients in a similar manner in myocytes from control and STZ-treated rats. However, the effect of halothane on the amplitude of shortening and L-type Ca2+ current was more pronounced in myocytes from STZ-treated animals compared to age-matched controls. Myofilament sensitivity to Ca2+ was significantly (p<0.01) increased in myocytes from STZ-treated rats compared to control. However, in the presence of halothane the myofilament sensitivity to Ca2+ was significantly (p<0.05) reduced to a greater extent in myocytes from STZ-treated rats compared to controls. In conclusion, these results show that contractility, Ca2+ transport and myofilament sensitivity were all altered in myocytes from STZ-treated rats and these processes were further altered in the presence of halothane suggesting that hearts from STZ-induced diabetic rats are sensitive to halothane.
AB - General anaesthetics have previously been shown to have profound effects on myocardial function. Moreover, many patients suffering from diabetes mellitus are anaesthetised during surgery. This study investigated compromised functioning of cardiac myocytes from streptozotocin (STZ)-induced diabetic rats and the additive effects of halothane on these dysfunctions. Ventricular myocytes were isolated from 8 to 12 weeks STZ-treated rats. Contraction and intracellular free calcium concentration ([Ca2+]i) were measured in electrically field-stimulated (1 Hz) fura-2-AM-loaded cells using a video-edge detection system and a fluorescence photometry system, respectively. L-type Ca2+ current was measured in whole cell, voltage-clamp mode. Halothane significantly (p<0.01) depressed the amplitude and the time course of the Ca2+ transients in a similar manner in myocytes from control and STZ-treated rats. However, the effect of halothane on the amplitude of shortening and L-type Ca2+ current was more pronounced in myocytes from STZ-treated animals compared to age-matched controls. Myofilament sensitivity to Ca2+ was significantly (p<0.01) increased in myocytes from STZ-treated rats compared to control. However, in the presence of halothane the myofilament sensitivity to Ca2+ was significantly (p<0.05) reduced to a greater extent in myocytes from STZ-treated rats compared to controls. In conclusion, these results show that contractility, Ca2+ transport and myofilament sensitivity were all altered in myocytes from STZ-treated rats and these processes were further altered in the presence of halothane suggesting that hearts from STZ-induced diabetic rats are sensitive to halothane.
KW - Calcium
KW - Contraction
KW - Diabetes mellitus
KW - Halothane
KW - Heart
KW - Streptozotocin
KW - Ventricular myocytes
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U2 - 10.1023/B:MCBI.0000028763.15680.07
DO - 10.1023/B:MCBI.0000028763.15680.07
M3 - Article
C2 - 15362511
AN - SCOPUS:3442879542
SN - 0300-8177
VL - 261
SP - 251
EP - 261
JO - Molecular and cellular biochemistry
JF - Molecular and cellular biochemistry
IS - 1
ER -