Modulation of Mitochondrial ATP-Dependent K⁺ Channels by Protein Kinase C

From the Section of Molecular and Cellular Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Md.

Correspondence to Eduardo Marbán, MD, PhD, Section of Molecular and Cellular Cardiology, Department of Medicine, Johns Hopkins University, Ross 844/720 Rutland Ave, Baltimore, MD 21205. E-mail marban{at}welchlink.welch.jhu.edu

Abstract—Pharmacological openers of mitochondrial ATP-dependent K⁺ (mitoK_ATP) channels mimic ischemic preconditioning, and such cardioprotection can be prevented by mitoK_ATP channel blockers. It is also known that protein kinase C (PKC) plays a key role in the induction and maintenance of preconditioning. To look for possible mechanistic links between these 2 sets of observations, we measured mitochondrial matrix redox potential as an index of mitoK_ATP channel activity in rabbit ventricular myocytes. The mitoK_ATP channel opener diazoxide (100 µmol/L) partially oxidized the matrix redox potential. Exposure to phorbol 12-myristate 13-acetate (PMA, 100 nmol/L) potentiated and accelerated the effect of diazoxide. These effects of PMA were blocked by the mitoK_ATP channel blocker 5-hydroxydecanoate, which we verified to be a selective blocker of the mitoK_ATP channel in simultaneous recordings of membrane current and flavoprotein fluorescence. The inactive control compound 4-phorbol (100 nmol/L) did not alter the effects of diazoxide. We conclude that the activity of mitoK_ATP channels can be regulated by PKC in intact heart cells. Potentiation of mitoK_ATP channel opening by PKC provides a direct mechanistic link between the signal transduction of ischemic preconditioning and pharmacological cardioprotection targeted at ATP-dependent K⁺ channels.

Key Words: diazoxide • preconditioning • protein kinase C • mitochondria • 5-hydroxydecanoate

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				O. Oldenburg, M. V Cohen, D. M Yellon, and J. M Downey Mitochondrial KATP channels: role in cardioprotection Cardiovasc Res, August 15, 2002; 55(3): 429 - 437. [Abstract] [Full Text] [PDF]

				J. Neckar, O. Szarszoi, L. Koten, F. Papousek, B. Ost'adal, G. J Grover, and F. Kolar Effects of mitochondrial KATP modulators on cardioprotection induced by chronic high altitude hypoxia in rats Cardiovasc Res, August 15, 2002; 55(3): 567 - 575. [Abstract] [Full Text] [PDF]

				Y.-P. Wang, H. Maeta, K. Mizoguchi, T. Suzuki, Y. Yamashita, and M. Oe Intestinal ischemia preconditions myocardium: role of protein kinase C and mitochondrial KATP channel Cardiovasc Res, August 15, 2002; 55(3): 576 - 582. [Abstract] [Full Text] [PDF]

				P. J Hanley, M. Mickel, M. Loffler, U. Brandt, and J. Daut KATP channel-independent targets of diazoxide and 5-hydroxydecanoate in the heart J. Physiol., August 1, 2002; 542(3): 735 - 741. [Abstract] [Full Text] [PDF]

				Y. Ohnuma, T. Miura, T. Miki, M. Tanno, A. Kuno, A. Tsuchida, and K. Shimamoto Opening of mitochondrial KATP channel occurs downstream of PKC-epsilon activation in the mechanism of preconditioning Am J Physiol Heart Circ Physiol, July 1, 2002; 283(1): H440 - H447. [Abstract] [Full Text] [PDF]

				H. Y. Zhang, B. C. McPherson, H. Liu, T. S. Baman, P. Rock, and Z. Yao H2O2 opens mitochondrial KATP channels and inhibits GABA receptors via protein kinase C-epsilon in cardiomyocytes Am J Physiol Heart Circ Physiol, April 1, 2002; 282(4): H1395 - H1403. [Abstract] [Full Text] [PDF]

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				C. P. Baines, J. Zhang, G.-W. Wang, Y.-T. Zheng, J. X. Xiu, E. M. Cardwell, R. Bolli, and P. Ping Mitochondrial PKC{epsilon} and MAPK Form Signaling Modules in the Murine Heart: Enhanced Mitochondrial PKC{epsilon}-MAPK Interactions and Differential MAPK Activation in PKC{epsilon}-Induced Cardioprotection Circ. Res., March 8, 2002; 90(4): 390 - 397. [Abstract] [Full Text] [PDF]

				A. Szewczyk and L. Wojtczak Mitochondria as a Pharmacological Target Pharmacol. Rev., March 1, 2002; 54(1): 101 - 127. [Abstract] [Full Text] [PDF]

				Z.-H. Shao, T. L. Vanden Hoek, Y. Qin, L. B. Becker, P. T. Schumacker, C.-Q. Li, L. Dey, E. Barth, H. Halpern, G. M. Rosen, et al. Baicalein attenuates oxidant stress in cardiomyocytes Am J Physiol Heart Circ Physiol, March 1, 2002; 282(3): H999 - H1006. [Abstract] [Full Text] [PDF]

				P. Korge, H. M. Honda, and J. N. Weiss Protection of cardiac mitochondria by diazoxide and protein kinase C: Implications for ischemic preconditioning PNAS, February 20, 2002; (2002) 52713199. [Abstract] [Full Text] [PDF]

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				Y. Wang, E. Takashi, M. Xu, A. Ayub, and M. Ashraf Downregulation of Protein Kinase C Inhibits Activation of Mitochondrial KATP Channels by Diazoxide Circulation, July 3, 2001; 104(1): 85 - 90. [Abstract] [Full Text] [PDF]

				Y. Toyoda, S. Levitsky, and J. D. McCully Opening of mitochondrial ATP-sensitive potassium channels enhances cardioplegic protection Ann. Thorac. Surg., April 1, 2001; 71(4): 1281 - 1288. [Abstract] [Full Text] [PDF]

				N. Sasaki, T. Sato, E. Marban, and B. O'Rourke ATP consumption by uncoupled mitochondria activates sarcolemmal KATP channels in cardiac myocytes Am J Physiol Heart Circ Physiol, April 1, 2001; 280(4): H1882 - H1888. [Abstract] [Full Text] [PDF]

				K. Mackay and D. Mochly-Rosen Arachidonic acid protects neonatal rat cardiac myocytes from ischaemic injury through {epsilon} protein kinase C Cardiovasc Res, April 1, 2001; 50(1): 65 - 74. [Abstract] [Full Text] [PDF]

				Z. Yao, B. C. McPherson, H. Liu, Z. Shao, C. Li, Y. Qin, T. L. Vanden Hoek, L. B. Becker, and P. T. Schumacker Signal transduction of flumazenil-induced preconditioning in myocytes Am J Physiol Heart Circ Physiol, March 1, 2001; 280(3): H1249 - H1255. [Abstract] [Full Text] [PDF]

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				C. Ozcan, E. L. Holmuhamedov, A. Jahangir, and A. Terzic Diazoxide protects mitochondria from anoxic injury: Implications for myopreservation J. Thorac. Cardiovasc. Surg., February 1, 2001; 121(2): 0298 - 306. [Abstract] [Full Text] [PDF]

				Y. Liu, G. Ren, B. O'Rourke, E. Marbán, and J. Seharaseyon Pharmacological Comparison of Native Mitochondrial KATP Channels with Molecularly Defined Surface KATP Channels Mol. Pharmacol., February 1, 2001; 59(2): 225 - 230. [Abstract] [Full Text]

				A. J. Kowaltowski, S. Seetharaman, P. Paucek, and K. D. Garlid Bioenergetic consequences of opening the ATP-sensitive K+ channel of heart mitochondria Am J Physiol Heart Circ Physiol, February 1, 2001; 280(2): H649 - H657. [Abstract] [Full Text] [PDF]

				E. Kevelaitis, A. Oubenaissa, C. Mouas, J. Peynet, and P. Menasche Ischemic preconditioning with opening of mitochondrial adenosine triphosphate-sensitive potassium channels or Na+/H+ exchange inhibition: Which is the best protective strategy for heart transplants? J. Thorac. Cardiovasc. Surg., January 1, 2001; 121(1): 0155 - 162. [Abstract] [Full Text] [PDF]

				S. Wang, J. Cone, and Y. Liu Dual roles of mitochondrial KATP channels in diazoxide-mediated protection in isolated rabbit hearts Am J Physiol Heart Circ Physiol, January 1, 2001; 280(1): H246 - H255. [Abstract] [Full Text] [PDF]

				S. Sanada, M. Kitakaze, H. Asanuma, K. Harada, H. Ogita, K. Node, S. Takashima, Y. Sakata, M. Asakura, Y. Shinozaki, et al. Role of mitochondrial and sarcolemmal KATP channels in ischemic preconditioning of the canine heart Am J Physiol Heart Circ Physiol, January 1, 2001; 280(1): H256 - H263. [Abstract] [Full Text] [PDF]

				G.-Y. Wang, S. Wu, J.-M. Pei, X.-C. Yu, and T.-M. Wong {kappa}- but not {delta}-opioid receptors mediate effects of ischemic preconditioning on both infarct and arrhythmia in rats Am J Physiol Heart Circ Physiol, January 1, 2001; 280(1): H384 - H391. [Abstract] [Full Text] [PDF]

				M. Tani, Y. Honma, H. Hasegawa, and K. Tamaki Direct activation of mitochondrial KATP channels mimics preconditioning but protein kinase C activation is less effective in middle-aged rat hearts Cardiovasc Res, January 1, 2001; 49(1): 56 - 68. [Abstract] [Full Text] [PDF]

				Y. Toyoda, I. Friehs, R. A. Parker, S. Levitsky, and J. D. McCully Differential role of sarcolemmal and mitochondrial KATP channels in adenosine-enhanced ischemic preconditioning Am J Physiol Heart Circ Physiol, December 1, 2000; 279(6): H2694 - H2703. [Abstract] [Full Text] [PDF]

				S. Ghosh, L. L Ng, S. Talwar, I. B Squire, and M. Galinanes Cardiotrophin-1 protects the human myocardium from ischemic injury: Comparison with the first and second window of protection by ischemic preconditioning Cardiovasc Res, December 1, 2000; 48(3): 440 - 447. [Abstract] [Full Text] [PDF]

				B. O'Rourke Pathophysiological and protective roles of mitochondrial ion channels J. Physiol., November 15, 2000; 529(1): 23 - 36. [Abstract] [Full Text] [PDF]

				B. O'Rourke Myocardial KATP Channels in Preconditioning Circ. Res., November 10, 2000; 87(10): 845 - 855. [Abstract] [Full Text] [PDF]

				S. Okubo, N. L. Bernardo, G. T. Elliott, M. L. Hess, and R. C. Kukreja Tyrosine kinase signaling in action potential shortening and expression of HSP72 in late preconditioning Am J Physiol Heart Circ Physiol, November 1, 2000; 279(5): H2269 - H2276. [Abstract] [Full Text] [PDF]

				Q. Zhang and Z. Yao Flumazenil preconditions cardiomyocytes via oxygen radicals and KATP channels Am J Physiol Heart Circ Physiol, October 1, 2000; 279(4): H1858 - H1863. [Abstract] [Full Text] [PDF]

				M. Kitakaze, K. Node, H. Asanuma, S. Takashima, Y. Sakata, M. Asakura, S. Sanada, Y. Shinozaki, H. Mori, T. Kuzuya, et al. Protein Tyrosine Kinase Is Not Involved in the Infarct Size-Limiting Effect of Ischemic Preconditioning in Canine Hearts Circ. Res., August 18, 2000; 87(4): 303 - 308. [Abstract] [Full Text] [PDF]

				H. Tong, W. Chen, C. Steenbergen, and E. Murphy Ischemic Preconditioning Activates Phosphatidylinositol-3-Kinase Upstream of Protein Kinase C Circ. Res., August 18, 2000; 87(4): 309 - 315. [Abstract] [Full Text] [PDF]

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				T. Sato, N. Sasaki, B. O'Rourke, and E. Marban Adenosine Primes the Opening of Mitochondrial ATP-Sensitive Potassium Channels : A Key Step in Ischemic Preconditioning? Circulation, August 15, 2000; 102(7): 800 - 805. [Abstract] [Full Text] [PDF]

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				R. M. Fryer, A. K. Hsu, H. Nagase, and G. J. Gross Opioid-Induced Cardioprotection against Myocardial Infarction and Arrhythmias: Mitochondrial versus Sarcolemmal ATP-Sensitive Potassium Channels J. Pharmacol. Exp. Ther., August 1, 2000; 294(2): 451 - 457. [Abstract] [Full Text]

				R. A. Hopper, C. R. Forrest, H. Xu, A. Zhong, W. He, J. Rutka, P. Neligan, and C. Y. Pang Role and mechanism of PKC in ischemic preconditioning of pig skeletal muscle against infarction Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2000; 279(2): R666 - R676. [Abstract] [Full Text] [PDF]

				T. Miki, T. Miura, A. Tsuchida, A. Nakano, T. Hasegawa, T. Fukuma, and K. Shimamoto Cardioprotective Mechanism of Ischemic Preconditioning Is Impaired by Postinfarct Ventricular Remodeling Through Angiotensin II Type 1 Receptor Activation Circulation, July 25, 2000; 102(4): 458 - 463. [Abstract] [Full Text] [PDF]

				P. E. Light, C. Bladen, R. J. Winkfein, M. P. Walsh, and R. J. French Molecular basis of protein kinase C-induced activation of ATP-sensitive potassium channels PNAS, July 19, 2000; (2000) 160068997. [Abstract] [Full Text]

				J. Seharaseyon, N. Sasaki, A. Ohler, T. Sato, H. Fraser, D. C. Johns, B. O'Rourke, and E. Marban Evidence against Functional Heteromultimerization of the KATP Channel Subunits Kir6.1 and Kir6.2 J. Biol. Chem., June 2, 2000; 275(23): 17561 - 17565. [Abstract] [Full Text] [PDF]

				T. Sato, N. Sasaki, J. Seharaseyon, B. O'Rourke, and E. Marban Selective Pharmacological Agents Implicate Mitochondrial but Not Sarcolemmal KATP Channels in Ischemic Cardioprotection Circulation, May 23, 2000; 101(20): 2418 - 2423. [Abstract] [Full Text] [PDF]

				E. J. Griffiths Mitochondria -- potential role in cell life and death Cardiovasc Res, April 1, 2000; 46(1): 24 - 27. [Full Text] [PDF]

				T. L. V. Hoek, L. B. Becker, Z.-H. Shao, C.-Q. Li, and P. T. Schumacker Preconditioning in Cardiomyocytes Protects by Attenuating Oxidant Stress at Reperfusion Circ. Res., March 17, 2000; 86(5): 541 - 548. [Abstract] [Full Text] [PDF]

				S. Ghosh, N. B Standen, and M. Galinanes Evidence for mitochondrial KATP channels as effectors of human myocardial preconditioning Cardiovasc Res, March 1, 2000; 45(4): 934 - 940. [Abstract] [Full Text] [PDF]

				T. Sato, N. Sasaki, B. O'Rourke, and E. Marban Nicorandil, a potent cardioprotective agent, acts by opening mitochondrial ATP-dependent potassium channels J. Am. Coll. Cardiol., February 1, 2000; 35(2): 514 - 518. [Abstract] [Full Text] [PDF]

				N. Sasaki, T. Sato, A. Ohler, B. O’Rourke, and E. Marban Activation of Mitochondrial ATP-Dependent Potassium Channels by Nitric Oxide Circulation, February 1, 2000; 101(4): 439 - 445. [Abstract] [Full Text] [PDF]

				T. Miura, Y. Liu, H. Kita, T. Ogawa, and K. Shimamoto Roles of mitochondrial ATP-sensitive K channels and PKC in anti-infarct tolerance afforded by adenosine A1 receptor activation J. Am. Coll. Cardiol., January 1, 2000; 35(1): 238 - 245. [Abstract] [Full Text] [PDF]

				R. M. Fryer, J. T. Eells, A. K. Hsu, M. M. Henry, and G. J. Gross Ischemic preconditioning in rats: role of mitochondrial KATP channel in preservation of mitochondrial function Am J Physiol Heart Circ Physiol, January 1, 2000; 278(1): H305 - H312. [Abstract] [Full Text] [PDF]

				T. Sato Signaling in Late Preconditioning : Involvement of Mitochondrial KATP Channels Circ. Res., December 3, 1999; 85(12): 1113 - 1114. [Full Text] [PDF]

				R. Ockaili, V. R. Emani, S. Okubo, M. Brown, K. Krottapalli, and R. C. Kukreja Opening of mitochondrial KATP channel induces early and delayed cardioprotective effect: role of nitric oxide Am J Physiol Heart Circ Physiol, December 1, 1999; 277(6): H2425 - H2434. [Abstract] [Full Text] [PDF]