Abstract
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. (Mol Cell Biochem 261: 251–261, 2004)
Similar content being viewed by others
References
Davies LA, Hamilton DL, Hopkins PM, Boyett MR, Harrison SM: Concentration-dependent inotropic effects of halothane, isoflurane and sevoflurane on rat ventricular myocytes. Br J Anaesth 82: 723–730, 1999
Harrison SM, Robinson M, Davies LA, Hopkins PM, Boyett MR: Mechanisms underlying the inotropic action of halothane on intact rat ventricular myocytes. Br J Anaesth 82: 609–621, 1999
Bosnjak ZJ, Supan FD, Rusch NJ: The effects of halothane, enflurane, and isoflurane on calcium current in isolated canine ventricular cells. Anesthesiology 74: 340–345, 1991
Ikemoto Y, Yatani A, Imoto Y, Arimura H: Reduction in the myocardial sodium current by halothane and thiamylal. Jpn J Physiol 36: 107–121, 1986
Mangano DT, Goldman L: Preoperative assessment of patients with known or suspected coronary disease. N Engl J Med 333: 1750–1756, 1995
Dhalla NS, Pierce GN, Innes IR, Beamish RE: Pathogenesis of cardiac dysfunction in diabetes mellitus. Can J Cardiol 1: 263–281, 1985
Pandit SV, Giles WR, Demir SS: A mathematical model of the electrophysiological alterations in rat ventricular myocytes in type-I diabetes. Biophys J 84: 832–841, 2003
Ren J, Davidoff AJ: Diabetes rapidly induces contractile dysfunction in isolated ventricular myocytes. Am J Physiol 272(suppl1): H148–H158, 1997
Choi KM, Zhong Y, Hoit BD, Grupp IL, Hahn H, Dilly KW, Guatimosim S, Lederer WJ, Matlib MA: Defective intracellular Ca2+ signaling contributes to cardiomyopathy in type 1 diabetic rats. Am J Physiol Heart Circ Physiol 283: H1398–H1408, 2002
Howarth FC, Qureshi MA, White E: Effects of hyperosmotic shrinking on ventricular myocyte shortening and intracellular Ca2+ in streptozotocin-induced diabetic rats. Pflugers Arch 444: 446–451, 2002
Howarth FC, Calaghan SC, Boyett MR, White E: Effect of the microtubule polymerizing agent taxol on contraction, Ca2+ transient and L-type Ca2+ current in rat ventricular myocytes. J Physiol 516: 409–419, 1999
Frampton JE, Orchard CH, Boyett MR: Diastolic, systolic and sarcoplasmic reticulum [Ca2+]i during inotropic interventions in isolated rat myocytes. J Physiol 437: 351–375, 1991
Hamill OP, Marty A, Neher E, Sakman B, Sigworth FJ: Improved patch clamp tool for high resolution current recordings from cells and cell free membrane patches. Pflugers Arch 398: 85–100, 1981
Brown AM, Lee KS, Powell T: Sodium current in single rat heart muscle cells. J Physiol 318: 479–500, 1981
Levi AJ, Hancox JC, Howarth FC, Croker J, Vinnicombe J: A method for making rapid changes of superfusate whilst maintaining temperature at 37 degrees C. Pflugers Arch 432: 930–937, 1996
London B, Krueger JW: Contraction in voltage-clamped, internally perfused single heart cells. J Gen Physiol 88: 475–505, 1986
Vornanen M, Shepherd N, Isenberg G: Tension-voltage relations of single myocytes reflect Ca release triggered by Na/Ca exchange at 35 degrees C but not 23 degrees C. Am J Physiol 267: C623–C632, 1994
Levi AJ, Hancox JC, Howarth FC, Croker J, Vinnicombe J: A method for making rapid changes of superfusate whilst maintaining temperature at 37 degrees C. Pflugers Arch 432: 930–937, 1996
Spurgeon HA, duBell WH, Stem MD, Sollett SJ, Ziman BD, Silverman HS, Capogossi MC, Talo A, Lakatti EG: Cytosolic calcium and myofilament in single rat cardiac myocytes achieve dynamic equilibrium during twitch relaxation. J Physiol 447: 83–102, 1992
Ren J, Bode AM: Altered cardiac excitation contraction coupling in ventricular myocytes from spontaneous diabetic BB rats. Am J Physiol Heart Circ Physiol 279(suppl1): H238–H244, 2000
Graham M, Qureshi MA, Harrison SM, Howarth FC: Effects of volatile anesthetics on contraction in ventricular myocytes from streptozotocin-induced rat. Mol Cell Biochem (this issue), 2003
Jenkins A, Franks NP, Lieb WR: Effects of temperature and volatile anesthetics on GABA-A receptor. Anesthesiology 90:2, 484–491, 1999
MacIver MB, Roth SH: Inhalation anaesthetics exhibit pathway specific and differential actions on hippocampal synaptic responses in vitro. Br J Anaesth 60: 680–691, 1988
Hebbar L, Dorman BH, Clair MJ, Roy RC, Spinale FG: Negative and selective effects of propofol on isolated swine myocyte contractile function in pacing-induced congestive heart failure. Anesthesiology 86(suppl 3): 649–659, 1997
Sprung J, Ogletree-Hughes ML, McConnell BK, Zakhary DR, Smolsky SM, Moravec CS: Effects of propofol on the contractility of failing and non-failing human heart muscle. Anesth Analg 93(suppl 3): 550–559, 2001
Piacentino V, Dipla K, Gaughan JP, Houser SR: Voltage-dependent calcium release from the SR of feline myocytes is explained by calcium-induced calcium release. J Physiol 523: 533–548, 2000
O'Rourke B, Kass DA, Tanaselli GF, Kaek S, Tunin R, Marban E: Mechanism of altered excitation contraction coupling in canine tachycardia-induced heart failure. Circ Res 84: 562–570, 1999
Litwin SE, Zhnag D, Bridge JH: Dyssynchronisation of calcium sparks in myocytes from infracted hearts. Circ Res 87: 1040–1048, 2000
Hofman PA, Menan V, Gannaway KF: Effects of diabetes on isometric tension as a function of [Ca2+]i and pH in cardiac myocytes. Am J Physiol 269(suppl 5): H1656–H1663, 1995
Howarth FC, Calaghan SC, Boyett MR, White E: Effect of the microtubule polymerising agent taxol on contraction, Ca2+ transient and L-type Ca2+ current in rat ventricular myocytes. J Physiol 516: 409–419, 1999
Bartunek AE, Claes VA, Housmans PR: Effect of volatile anesthetics on stiffness of mammalian ventricular muscle. J Appl Physiol 91: 1563–1573, 2001
Housmans PR, Wanek LA, Carton EG, Bartunek AE: Effects of halothane and isoflurane and intracellular calcium transient in ferret cardiac myocytes. Anesthesiology 93: 189–201, 2000
Hunneke R, Jungling E, Shasa M, Kossaint K, Luckoff J: Effects of anaesthetic gases xenon, halothane and isoflurane on calcium and potassium currents in human atrial cardiomyocytes. Anesthesiology 95: 999–1006, 2001
Kamatchi GL, Duneux ME, Lynch C: Differential sensitivity of expressed L-type calcium channel and M1 muscarinic receptor to volatile anesthetic in Xenopus oocytes. Pharmacol Exp Ther 297: 981–990, 2001
Eskinder H, Rusch NJ, Sunan FD, Kampine JP, Bosnjak ZJ: The effects of volatile anaesthetics on L and T-type calcium currents in canine Purkinje cells. Anesthesiology 74: 919–926, 1991
Arikawa M, Takahashi N, Kira T, Hara M, Saikawa T, Sakata T: Enhanced inhibition of L-type currents by troglitazone in streptozotocin-induced diabetic rat cardiac ventricular myocytes. Br J Pharmacol 136: 803–810, 2002
Murkherjee J, Hewett KW, Walker JD, Basler CA, Spinale FG: Changes in L-type calcium channel abundance and function during transition to pacing heart-induced congestive heart failure. Cardiovasc Res 37: 432–444, 1998
Santos PE, Barcellos LC, Mill JG, Masuda M: Ventricular action potential and L-type calcium channel in infarct-induced hypertrophy. J Cardiovasc Electrophysiol 6: 1004–1014, 1995
Van der Velden J, Papp Z, Zaremb R, Boontje NM, de Jong JW, Owen VJ, Burton PB, Goldman P, Jaquet K, Stiemen GJ: Increased calcium sensitivity of contractile apparatus in human heart failure results from altered phosphorylation of contractile proteins. Cardiovasc Res 57: 37–47, 2003
Brixius K, Savvido-Zaroti P, Mehlhom V, Block W, Kranais EG, Schwinger PH: Increased calcium sensitivity of myofibrillar tension in heart failure and its function importance. Bas Res Cardiol 97(suppl): 11–117, 2002
Malkatra A, Reich D, Nakouzi A, Sanghi V, Geenan DL, Buttrick PM: Experimental diabetes is associated with functional activation of PKC and phosporylation of Tn1 in heart. Circ Res 81: 1027–1033, 1997
Kim HW, Ch YS, Lee HR, Park SY, Kim YH: Diabetic alterations in cardiac sarcoplasmic reticulum Ca2+-ATPase and phospholamban protein expression. Life Sci 70: 367–379, 2001
Teshima Y, Takahashi N, Saikawa T, Hara M, Yasunaga S, Hidaka S, Sakata T: Diminished expression of sarcoplasmic reticulum Ca2+-ATPase and ryanodine sensitive Ca2+ channel mRNA in streptozotocin-induced diabetic rat heart. J Mol Cell Cardiol 32: 655–664, 2000
Kanaya N, Gable B, Murray PA, Damron DS: Propofol increases phosphorylation of troponin 1 and myosin light chain 2 via protein kinase C activity in cardiomyocyates. Anesthesiology 98: 1363–1371, 2003
Nakae Y, Fujita S, Nariki A: Modification of myofilament calcium desensitivity by delta and kappa opioid agonists in intact guinea pig hearts. Anesth Analg 96: 733–739, 2003
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Woodall, A., Bracken, N., Qureshi, A. et al. Halothane alters contractility and Ca2+ transport in ventricular myocytes from streptozotocin-induced diabetic rats. Mol Cell Biochem 261, 251–261 (2004). https://doi.org/10.1023/B:MCBI.0000028763.15680.07
Issue Date:
DOI: https://doi.org/10.1023/B:MCBI.0000028763.15680.07