Cardiac Impulse Propagation

Figures

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  Figure 1. Gap Junction Coupling and Conduction (A) Cx43 expression (green) in normal mouse ventricular tissue. Red is background staining. (B) Cx43 expression (green) in Cx43 KO mouse ventricular tissue. (C) CV and AR from normal (black) and Cx43 KO (open) mice. CVmax is for the longitudinal direction and CVmin is for the transverse direction. (A)-(C) were adapted from Gutstein et a,9 with permission. (D) CV vs Cx43 expression level in Cx43 KO mouse ventricles (colored circles). The CV and Cx43 abundance were set as 100% for normal control (black circle). Those of KO mice are percentages of normal control (data from Supplemental Table 1). Gray curve is the prediction of the continuous cable theory of gap junction coupling (Equation 1), normalized to control, that is, simply set Equation 1 to CV=g and vary g from 0 to 1. AR = anisotropic ratio; CNTRL = control; Cx43 = connexin 43; CV = conduction velocity; KO = knockout.

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  Figure 2. Ephaptic and Gap Junction Coupling (A) Schematic diagram illustrating ephaptic and gap junction coupling. ϕi is the intracellular potential, ϕe is the bulk extracellular potential, which is grounded, and ϕc is the potential in the cleft that is grounded at resting but becomes negative when cells depolarize. INa is the Na+ current located on both the junctional and lateral membrane. ILat is the total current on the lateral membrane except INa. IC is the current flow from the bulk extracellular space to the cleft. IGap is the gap junction current. (B) Steady-state activation curve of INa. (C) CV vs cleft width for different gap junction strengths from a computer simulation.56 Gap junction conductance is labeled as gj with values indicated by different symbols. The shaded region is where gap junction coupling and ephaptic coupling are in synergy, CV is larger than that by either alone. The red arrow marks a hypothetical Cx43 KO case when ephaptic coupling is present. The green arrow marks a hypothetical Cx43 KO case when ephaptic coupling is absent (noncleft model). Abbreviations as in Figure 1.

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  Figure 3. ID and Perinexus (A) An electron microscopy image of the stair-like intercalated disc (ID) between 2 cells as indicated by the labels. Modified from M.A. Hill.94 (B) Transmission electron microscopy image of an ID segment between 2 adjacent cells in an adult murine heart showing gap junctions (labeled as “GJ”), desmosomes (labeled as “D”), and mitochondria (labeled as “M”). The red arrow points to a perinexal segment. Adapted from Delmar and Liang,65 with permission. (C) Schematic diagram of an ID model composed of a GJ segment, a perinexal segment, and a desmosome segment.

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  Figure 4. CV and APD Changes Caused by Osmotic Agents (A) Upper: Sample images of perinexi (yellow) under different osmotic agents. Lower: The width of perinexi (Wp) measured under different osmotic agents. (B) Schematic plot of CV changes vs Wp under different osmotic agents labeled. Arrows indicate alterations by the agents. (C) Perinexal separation assessed by transmission electron microscopy is increased by acute interstitial edema (AIE) (green) independent of ATXII relative to AIE and ATXII+AIE. (D) Action potential duration (APD) as a function of cycle length for control (CTRL) (black), AIE (green), ATXII (blue), and ATXII+AIE (red) experiments. A was adapted from and B plotted based on the results reported by Adams et al,30 with permission. C and D were adapted from Greer-Short et al,59 with permission. Abbreviation as in Figure 1.

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  Central Illustration. Mechanisms of Myocyte Coupling and Cardiac Conduction