Anisotropic conduction in monolayers of neonatal rat heart cells cultured on collagen substrate

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Circulation Research. 1994;75:591-595

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ARTICLES

Anisotropic conduction in monolayers of neonatal rat heart cells cultured on collagen substrate

VG Fast and AG Kleber
Department of Physiology, University of Berne, Switzerland.

Anisotropic impulse conduction was studied in neonatal rat heart cell monolayers produced by culturing cells on a growth-directing substrate of collagen. Monolayers consisting of parallel-oriented cells without visible intercellular clefts were selected for experiments; cell lengths and widths were 65.8 +/- 12.5 and 12.2 +/- 3.2 microns (n = 49), respectively. Action potential upstrokes were measured by using 12 photodiodes selected within a 10x10 diode array and a voltage-sensitive dye (RH-237). The size of the area sensed by a single diode was 14 x 14 microns. High-density multiple recordings (resolution, up to 15 microns) demonstrated the variability of local activation delays and of the maximal rate of rise of the action potential upstroke (Vmax), which are presumably related to the microscopic cellular architecture. Mean macroscopic conduction velocities measured over distances of 135 microns were 34.6 +/- 4.5 and 19.0 +/- 4.3 cm/s (mean +/- SD, n = 13, P < .0001) in longitudinal and transverse directions, respectively. The anisotropic velocity ratio was 1.89 +/- 0.38 (n = 13). Mean Vmax was not significantly different in two directions (122.0 +/- 17.4 V/s longitudinally versus 125.2 +/- 15.6 V/s transversely, n = 13, P = NS). In conclusion, we developed an anisotropic cell culture model suitable for studying impulse conduction with cellular resolution. The anisotropic velocity ratio was close to values measured in vivo. By contrast, Vmax was not dependent on the direction of propagation.

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				R. C. Pimentel, K. A. Yamada, A. G. Kleber, and J. E. Saffitz Autocrine Regulation of Myocyte Cx43 Expression by VEGF Circ. Res., April 5, 2002; 90(6): 671 - 677. [Abstract] [Full Text] [PDF]

				Y. Feld, M. Melamed-Frank, I. Kehat, D. Tal, S. Marom, and L. Gepstein Electrophysiological Modulation of Cardiomyocytic Tissue by Transfected Fibroblasts Expressing Potassium Channels: A Novel Strategy to Manipulate Excitability Circulation, January 29, 2002; 105(4): 522 - 529. [Abstract] [Full Text] [PDF]

				S. P. Thomas, L. Bircher-Lehmann, S. A. Thomas, J. Zhuang, J. E. Saffitz, and A. G. Kleber Synthetic Strands of Neonatal Mouse Cardiac Myocytes : Structural and Electrophysiological Properties Circ. Res., September 15, 2000; 87(6): 467 - 473. [Abstract] [Full Text] [PDF]

				J. Zhuang, K. A. Yamada, J. E. Saffitz, and A. G. Kleber Pulsatile Stretch Remodels Cell-to-Cell Communication in Cultured Myocytes Circ. Res., August 18, 2000; 87(4): 316 - 322. [Abstract] [Full Text] [PDF]

				R. W. Joyner, Y.-G. Wang, R. Wilders, D. A. Golod, M. B. Wagner, R. Kumar, and W. N. Goolsby A spontaneously active focus drives a model atrial sheet more easily than a model ventricular sheet Am J Physiol Heart Circ Physiol, August 1, 2000; 279(2): H752 - H763. [Abstract] [Full Text] [PDF]

				V. G. Fast, S. Rohr, and R. E. Ideker Nonlinear changes of transmembrane potential caused by defibrillation shocks in strands of cultured myocytes Am J Physiol Heart Circ Physiol, March 1, 2000; 278(3): H688 - H697. [Abstract] [Full Text] [PDF]

				M. S. Spach, J. F. Heidlage, P. C. Dolber, and R. C. Barr Electrophysiological Effects of Remodeling Cardiac Gap Junctions and Cell Size : Experimental and Model Studies of Normal Cardiac Growth Circ. Res., February 18, 2000; 86(3): 302 - 311. [Abstract] [Full Text] [PDF]

				Y.-G. Wang, R. Kumar, M. B. Wagner, R. Wilders, D. A. Golod, W. N. Goolsby, and R. W. Joyner Electrical interactions between a real ventricular cell and an anisotropic two-dimensional sheet of model cells Am J Physiol Heart Circ Physiol, February 1, 2000; 278(2): H452 - H460. [Abstract] [Full Text] [PDF]

				J. P. Kucera, A. G. Kleber, and S. Rohr Slow Conduction in Cardiac Tissue, II : Effects of Branching Tissue Geometry Circ. Res., October 19, 1998; 83(8): 795 - 805. [Abstract] [Full Text] [PDF]

				C. J. Hyatt, J. J. Lemasters, B. J. Muller-Borer, T. A. Johnson, and W. E. Cascio A superfusion system to study border zones in confluent cultures of neonatal rat heart cells Am J Physiol Heart Circ Physiol, June 1, 1998; 274(6): H2001 - H2008. [Abstract] [Full Text] [PDF]

				V. G. Fast, S. Rohr, A. M. Gillis, and A. G. Kleber Activation of Cardiac Tissue by Extracellular Electrical Shocks : Formation of `Secondary Sources' at Intercellular Clefts in Monolayers of Cultured Myocytes Circ. Res., February 23, 1998; 82(3): 375 - 385. [Abstract] [Full Text] [PDF]

				R. M. Shaw and Y. Rudy Ionic Mechanisms of Propagation in Cardiac Tissue : Roles of the Sodium and L-type Calcium Currents During Reduced Excitability and Decreased Gap Junction Coupling Circ. Res., November 19, 1997; 81(5): 727 - 741. [Abstract] [Full Text]

				A. M. Gillis, V. G. Fast, S. Rohr, and A. G. Kleber Spatial Changes in Transmembrane Potential During Extracellular Electrical Shocks in Cultured Monolayers of Neonatal Rat Ventricular Myocytes Circ. Res., October 1, 1996; 79(4): 676 - 690. [Abstract] [Full Text]

				B. J. Darrow, V. G. Fast, A. G. Kleber, E. C. Beyer, and J. E. Saffitz Functional and Structural Assessment of Intercellular Communication: Increased Conduction Velocity and Enhanced Connexin Expression in Dibutyryl cAMP�Treated Cultured Cardiac Myocytes Circ. Res., August 1, 1996; 79(2): 174 - 183. [Abstract] [Full Text]

				V. G. Fast, B. J. Darrow, J. E. Saffitz, and A. G. Kleber Anisotropic Activation Spread in Heart Cell Monolayers Assessed by High-Resolution Optical Mapping: Role of Tissue Discontinuities Circ. Res., July 1, 1996; 79(1): 115 - 127. [Abstract] [Full Text]

				J. Fleischhauer, L. Lehmann, and A. G. Kleber Electrical Resistances of Interstitial and Microvascular Space as Determinants of the Extracellular Electrical Field and Velocity of Propagation in Ventricular Myocardium Circulation, August 1, 1995; 92(3): 587 - 594. [Abstract] [Full Text]