Differential regulation of distinct types of gap junction channels by similar phosphorylating conditions

BR Kwak, MM Hermans, HR De Jonge, SM Lohmann, HJ Jongsma and M Chanson

Department of Medical Physiology and Sports Medicine, Utrecht University, The Netherlands.

Studies on physiological modulation of intercellular communication mediated by protein kinases are often complicated by the fact that cells express multiple gap junction proteins (connexins; Cx). Changes in cell coupling can be masked by simultaneous opposite regulation of the gap junction channel types expressed. We have examined the effects of activators and inhibitors of protein kinase A (PKA), PKC, and PKG on permeability and single channel conductance of gap junction channels composed of Cx45, Cx43, or Cx26 subunits. To allow direct comparison between these Cx, SKHep1 cells, which endogenously express Cx45, were stably transfected with cDNAs coding for Cx43 or Cx26. Under control conditions, the distinct types of gap junction channels could be distinguished on the basis of their permeability and single channel properties. Under various phosphorylating conditions, these channels behaved differently. Whereas agonists/antagonist of PKA did not affect permeability and conductance of all gap junction channels, variable changes were observed under PKC stimulation. Cx45 channels exhibited an additional conductance state, the detection of the smaller conductance states of Cx43 channels was favored, and Cx26 channels were less often observed. In contrast to the other kinases, agonists/antagonist of PKG affected permeability and conductance of Cx43 gap junction channels only. Taken together, these results show that distinct types of gap junction channels are differentially regulated by similar phosphorylating conditions. This differential regulation may be of physiological importance during modulation of cell-to-cell communication of more complex cell systems.

Volume 6, Issue 12, pp. 1707-1719, 12/01/1995
Copyright © 1995 by The American Society for Cell Biology

This article has been cited by other articles:

				A. Salameh, S. Krautblatter, S. Baessler, S. Karl, D. R. Gomez, S. Dhein, and D. Pfeiffer Signal Transduction and Transcriptional Control of Cardiac Connexin43 Up-Regulation after {alpha}1-Adrenoceptor Stimulation J. Pharmacol. Exp. Ther., July 1, 2008; 326(1): 315 - 322. [Abstract] [Full Text] [PDF]

				B. Rodenwaldt, U. Pohl, and C. de Wit Endogenous and exogenous NO attenuates conduction of vasoconstrictions along arterioles in the microcirculation Am J Physiol Heart Circ Physiol, May 1, 2007; 292(5): H2341 - H2348. [Abstract] [Full Text] [PDF]

				V. V. Matchkov, H. Gustafsson, A. Rahman, D. M. Briggs Boedtkjer, S. Gorintin, A. K. Hansen, E. V. Bouzinova, H. A. Praetorius, C. Aalkjaer, and H. Nilsson Interaction Between Na+/K+-Pump and Na+/Ca2+-Exchanger Modulates Intercellular Communication Circ. Res., April 13, 2007; 100(7): 1026 - 1035. [Abstract] [Full Text] [PDF]

				J. F. Ek-Vitorin and J. M. Burt Quantification of gap junction selectivity Am J Physiol Cell Physiol, December 1, 2005; 289(6): C1535 - C1546. [Abstract] [Full Text] [PDF]

				A. Hoffmann, T. Gloe, U. Pohl, and S. Zahler Nitric oxide enhances de novo formation of endothelial gap junctions Cardiovasc Res, November 1, 2003; 60(2): 421 - 430. [Abstract] [Full Text] [PDF]

				J. L. Solan, M. D. Fry, E. M. TenBroek, and P. D. Lampe Connexin43 phosphorylation at S368 is acute during S and G2/M and in response to protein kinase C activation J. Cell Sci., June 1, 2003; 116(11): 2203 - 2211. [Abstract] [Full Text] [PDF]

				G. T. Cottrell, R. Lin, B. J. Warn-Cramer, A. F. Lau, and J. M. Burt Mechanism of v-Src- and mitogen-activated protein kinase-induced reduction of gap junction communication Am J Physiol Cell Physiol, February 1, 2003; 284(2): C511 - C520. [Abstract] [Full Text] [PDF]

				B. R Kwak, D. C Shah, and F. Mach A starting point for structure function relationships in the canine pulmonary veins Cardiovasc Res, September 1, 2002; 55(4): 703 - 705. [Full Text] [PDF]

				N. Duval, D. Gomes, V. Calaora, A. Calabrese, P. Meda, and R. Bruzzone Cell coupling and Cx43 expression in embryonic mouse neural progenitor cells J. Cell Sci., August 15, 2002; 115(16): 3241 - 3251. [Abstract] [Full Text] [PDF]

				A. P. Moreno, M. Chanson, J. Anumonwo, I. Scerri, H. Gu, S. M. Taffet, and M. Delmar Role of the Carboxyl Terminal of Connexin43 in Transjunctional Fast Voltage Gating Circ. Res., March 8, 2002; 90(4): 450 - 457. [Abstract] [Full Text] [PDF]

				E. G. A. Harks, A. D. G. de Roos, P. H. J. Peters, L. H. de Haan, A. Brouwer, D. L. Ypey, E. J. J. van Zoelen, and A. P. R. Theuvenet Fenamates: A Novel Class of Reversible Gap Junction Blockers J. Pharmacol. Exp. Ther., September 1, 2001; 298(3): 1033 - 1041. [Abstract] [Full Text] [PDF]

				T. A.B. van Veen, H. V.M. van Rijen, and T. Opthof Cardiac gap junction channels: modulation of expression and channel properties Cardiovasc Res, August 1, 2001; 51(2): 217 - 229. [Abstract] [Full Text] [PDF]

				M. Chanson, P.-Y. Berclaz, I. Scerri, T. Dudez, K. Wernke-Dollries, L. Pizurki, A. Pavirani, M. A. Fiedler, and S. Suter Regulation of Gap Junctional Communication by a Pro-Inflammatory Cytokine in Cystic Fibrosis Transmembrane Conductance Regulator-Expressing but Not Cystic Fibrosis Airway Cells Am. J. Pathol., May 1, 2001; 158(5): 1775 - 1784. [Abstract] [Full Text] [PDF]

				F. J. Elcock, E. Deag, R. A. Roberts, and J. K. Chipman Nafenopin Causes Protein Kinase C-Mediated Serine Phosphorylation and Loss of Function of Connexin 32 Protein in Rat Hepatocytes without Aberrant Expression or Localization Toxicol. Sci., July 1, 2000; 56(1): 86 - 94. [Abstract] [Full Text] [PDF]

				P. D. Lampe, E. M. TenBroek, J. M. Burt, W. E. Kurata, R. G. Johnson, and A. F. Lau Phosphorylation of Connexin43 on Serine368 by Protein Kinase C Regulates Gap Junctional Communication J. Cell Biol., June 26, 2000; 149(7): 1503 - 1512. [Abstract] [Full Text] [PDF]

				T. A.B. van Veen, H. V.M. van Rijen, and H. J. Jongsma Electrical conductance of mouse connexin45 gap junction channels is modulated by phosphorylation Cardiovasc Res, June 1, 2000; 46(3): 496 - 510. [Abstract] [Full Text] [PDF]

				S.-P. Onn and A. A. Grace Amphetamine Withdrawal Alters Bistable States and Cellular Coupling in Rat Prefrontal Cortex and Nucleus Accumbens Neurons Recorded In Vivo J. Neurosci., March 15, 2000; 20(6): 2332 - 2345. [Abstract] [Full Text] [PDF]

				H. V.M. van Rijen, T. A.B. van Veen, M. M.P. Hermans, and H. J. Jongsma Human connexin40 gap junction channels are modulated by cAMP Cardiovasc Res, March 1, 2000; 45(4): 941 - 951. [Abstract] [Full Text] [PDF]

				A. Paulson, P. Lampe, R. Meyer, E TenBroek, M. Atkinson, T. Walseth, and R. Johnson Cyclic AMP and LDL trigger a rapid enhancement in gap junction assembly through a stimulation of connexin trafficking J. Cell Sci., January 9, 2000; 113(17): 3037 - 3049. [Abstract] [PDF]

				B. R. Kwak, M. J.A. van Kempen, M. Theveniau-Ruissy, D. B. Gros, and H. J. Jongsma Connexin expression in cultured neonatal rat myocytes reflects the pattern of the intact ventricle Cardiovasc Res, November 1, 1999; 44(2): 370 - 380. [Abstract] [Full Text] [PDF]

				S. Alcolea, M. Theveniau-Ruissy, T. Jarry-Guichard, I. Marics, E. Tzouanacou, J.-P. Chauvin, J.-P. Briand, A. F. M. Moorman, W. H. Lamers, and D. B. Gros Downregulation of Connexin 45 Gene Products During Mouse Heart Development Circ. Res., June 25, 1999; 84(12): 1365 - 1379. [Abstract] [Full Text] [PDF]

				A. Muller, M. Lauven, R. Berkels, S. Dhein, H.-R. Polder, and W. Klaus Switched single-electrode voltage-clamp amplifiers allow precise measurement of gap junction conductance Am J Physiol Cell Physiol, April 1, 1999; 276(4): C980 - C987. [Abstract] [Full Text] [PDF]

				C. G. Bevans, M. Kordel, S. K. Rhee, and A. L. Harris Isoform Composition of Connexin Channels Determines Selectivity among Second Messengers and Uncharged Molecules J. Biol. Chem., January 30, 1998; 273(5): 2808 - 2816. [Abstract] [Full Text] [PDF]

				S. Verheule, M. J. A. van Kempen, P. H. J. A. t. Welscher, B. R. Kwak, and H. J. Jongsma Characterization of Gap Junction Channels in Adult Rabbit Atrial and Ventricular Myocardium Circ. Res., May 19, 1997; 80(5): 673 - 681. [Abstract] [Full Text]

				E. M. TenBroek, P. D. Lampe, J. L. Solan, J. K. Reynhout, and R. G. Johnson Ser364 of connexin43 and the upregulation of gap junction assembly by cAMP J. Cell Biol., December 24, 2001; 155(7): 1307 - 1318. [Abstract] [Full Text] [PDF]

				A. P. Moreno, M. Chanson, J. Anumonwo, I. Scerri, H. Gu, S. M. Taffet, and M. Delmar Role of the Carboxyl Terminal of Connexin43 in Transjunctional Fast Voltage Gating Circ. Res., March 8, 2002; 90(4): 450 - 457. [Abstract] [Full Text] [PDF]