1. Volume 17, Issue 2, Pages 73-81 (April 2010)
Pathological remodeling of cardiac gap junction connexin 43—With special reference to arrhythmogenesis 
Issei Imanaga 
Pathophysiology 
Volume 17, Issue 2, Pages (April 2010)
DOI: /j.pathophys
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2. Fig. 1
Schematic representation of sequence of events generating ventricular tacyarrhythmias (ventricular fibrillation). EAD: early after depolarization, DAD: delayed after depolarization, AT1: angiotensin II-type 1 receptor. Note downward remodeling of Cx43 by angiotensin II.
Pathophysiology  , 73-81DOI: ( /j.pathophys )
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3. Fig. 2
Schematic representation of effects of angiotensin II on the generation of ventricular tacyarrhythmias (ventricular fibrillation). AT1: angiotensin II-type 1 receptor. Note upward remodeling of Cx43 by angiotensin II.
Pathophysiology  , 73-81DOI: ( /j.pathophys )
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4. Fig. 3
(Panel A) The output (the upper trace) and the monophasic action potentials recorded from the surface of the right ventricular wall (the lower trace) of the isolated rat heart with a suction electrode. The heart is perfused on a Langendorff apparatus. (a) control sinus rhythm, (b) flutter induced by aconitine (0.1μM), and (c) shift from the flutter to the fibrillation. (Panel B) The transmembrane action potentials recorded from an endocardial muscle strip isolated from the right ventricular free wall of the rat heart during the aconitine (0.1μM)-induced ventricular flutter (a) and fibrillation (b). Two glass microelectrodes are placed 200μm apart from each other. Note the synchronous electrical activities at the flutter and desynchronous electrical activities in the neighboring cells at the fibrillation. The flutter shifts spontaneously to the fibrillation. Details in the text. Aconitine was applied at a concentration of 0.1μM. The same phenomenon is observed on the Langendorff-perfusing heart. Modified from Figs. 1 and 2 in Ref. [13].
Pathophysiology  , 73-81DOI: ( /j.pathophys )
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5. Fig. 4
Confocal laser scan micrographs of the immunofluorescence of Cx43 (white spots) at the gap junction area in the intercalated disk of ventricular muscle cells of the rat heart (high magnification). (A) Normal control, (B) at the presence of cyclic AMP analog (8 bromo cyclic AMP 0.5μM, 90min); similar results are observed by PKA activator (1μM, 90min), (C) hypoxia 30–40min, (D) STZ (streptozotocin-induced) diabetic (Type I diabetic model); similar results are observed in OLETF or GK (Type II diabeic model), by PMA (0.1μM, 90min) and by Angiotensin II analog (0.1μM, 90min), (E) at the onset of the aconitine-induced ventricular fibrillation, and (F) at the advanced stage of the ventricular fibrillation (20min). Agents (cyclic AMP analog, PKA activator, PMA, angiotensin II) were applied to the Langendorff-perfusing heart. Modified from Refs. [13,14,30].
Pathophysiology  , 73-81DOI: ( /j.pathophys )
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6. Fig. 5
Western blot findings of Cx43 in the ventricular muscle of the rat heart showing the PKA-mediated phosphorylation isoform (P1) (Panel A) and the PKCɛ-mediated phosphorylation isoform (P2) (Panel B). P0 is non-phosphorylated isoform. P1 is augmented by cyclic AMP analog (8 bromo cyclic AMP 0.5μM, 90min) or PKA activator (1μM, 90min) and suppressed by hypoxia, intracellular Ca overload or intracellular acidosis. The ratio of P1/P0 indicates a level of the PKA-mediated phosphorylation. Modified from Figs. 3 and 6 in Ref. [14]. P2 is augmented by an activation of PKCɛ which is induced by angiotensin II analog (0.1μM, 90min), PMA (0.1μM, 90min), or Type I or Type II diabetic. The ratio of P2/P0 indicates a level of the PKC-mediated phsophorylation. Modified from Fig. 3 in Ref. [30].
Pathophysiology  , 73-81DOI: ( /j.pathophys )
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7. Fig. 6
Statistical analysis of the changes in ri (longitudinal internal resistance) (the upper panel) and the ratio of P1/P0 (the lower panel) during hypoxia and the effects of the presence of cyclic AMP analog (8 bromo cyclic AMP, 0.5μM) on them. The columns represent the relative value and 1.0 (white column) means the value of the control (normoxia, without cyclic AMP analog). Oblique lined columns indicate the value in the presence of cyclic AMP analog. Vertical bars represent the mean±SEM, *p<0.001 vs. the control and ▴p<0.001 vs. without cyclic AMP analog. Modified from Figs. 5 and 6 in Ref. [14].
Pathophysiology  , 73-81DOI: ( /j.pathophys )
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8. Fig. 7
Statistical analysis of the changes in the susceptibility of the heart to the ventricular fibrillation (VF) during hypoxia and the effects of the presence of cyclic AMP analog (8 bromo cyclic AMP, 0.5μM) on them. The susceptibility is evaluated by time of the shift from the flutter to the fibrillation. The columns represent the relative value 1.0 (white column) means value of the control (normoxia, without cyclic AMP analog). Oblique lined columns indicate the value in the presence of cyclic AMP analog. Vertical bars represent the mean±SEM, *p<0.001 vs. the control and ▴p<0.001 vs. without cyclic AMP analog. Partly modified from Table 1 in Ref. [13].
Pathophysiology  , 73-81DOI: ( /j.pathophys )
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9. Fig. 8
Western blot findings showing a comparison of expression of angiotensin II, PKCɛ and Cx43 between the normal (left lane) and the diabetic (right lane) heart. (Panel A) Cardiac tissue angiotensin II, (Panel B) PKCɛ, (Panel C) co-immunoprecipitation of Cx43 with PKCɛ. B and C, modified from Fig. 5 in Ref. [30].
Pathophysiology  , 73-81DOI: ( /j.pathophys )
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10. Fig. 9
Western blot findings of Cx43 in the ventricular muscle of the rat heart showing the signal from left to right lanes, before fibrillation (as control), at the onset of fibrillation and at a state of advanced fibrillation (20min), respectively. Alterations of the PKA-mediated phsophorylation isoform (P1) (Panel A), the PKC-mediated phosphorylation isoform (P2) (Panel B), cardiac tissue angiotensin II (Panel C) and PKCɛ (Panel D) are indicated. Note that the PKA-mediated phosphorylation is significantly suppressed, that the PKC-mediated phosphorylation is significantly augmented, and that angiotensin II and PKCɛ are significantly augmented, as the ventricular fibrillation advances. Modified from Figs. 4–6 in Ref. [13].
Pathophysiology  , 73-81DOI: ( /j.pathophys )
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11. Fig. 10
Statistical analysis of the effects of some factors on the susceptibility of the heart to the ventricular fibrillation (VF). The susceptibility is evaluated by time of shift from the flutter to the fibrillation. (A) Normal, (B) the presence of angiotensin II (0.1μM, 90min), (C) angiotensin II at the presence of AT1 inhibitor (1μM), (D) PMA (0.1μM, 90min), (E) PMA at the presence of PKC inhibitor (1μM), (F) streptozotocin-induced diabetic (type I diabetic model), and (G) OLETF or GK (type II diabetic model). Agents were applied to the Langendorff-perfusing heart. Vertical bars represent the mean±SEM, *p<0.001 vs. the normal (A). Modified from Table 1 in Ref. [13].
Pathophysiology  , 73-81DOI: ( /j.pathophys )
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12. Fig. 11
(Panel A) Western blot findings of Cx45 in the ventricular muscle of the rat heart showing the signal before fibrillation (as before), at the flutter stage, at the onset of the fibrillation and at a state of advanced fibrillation (20min). (Panel B) Confocal laser scan micrographs of the immunofluorescence of Cx45 (white spots) showing the signal before fibrillation (as before), at the onset of the fibrillation, at a state of advanced fibrillation (20min) and at a state of more advanced fibrillation (40min) (not published).
Pathophysiology  , 73-81DOI: ( /j.pathophys )
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