Characterization of novel arrhythmogenic patterns arising secondary to heterogeneous expression and activation of Nav1.8

Figures

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  Figure 1. Effect of A-803467 (3–1,000 nmol/L) administration on action potential properties in canine left ventricular epicardial cardiomyocytes (N = number of dogs; n = number of tissue slices). (A–F) Average data for action potential amplitude (APA), maximum diastolic potential (MDP), maximum rate of rise of the action potential upstroke (Vmax), action potential duration at 30%, 50% and 90% repolarization (APD30, APD50 and APD90), before (control) and after administration and washout of A-803467 (N = 5 and n = 5, respectively).

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  Figure 2. Effect of A-803467 (3–1,000 nmol/L) administration on action potential properties in canine left ventricular M cardiomyocytes (N = number of dogs; n = number of tissue slices). (A–F) Average data for action potential amplitude (APA), maximum diastolic potential (MDP), maximum rate of rise of the action potential upstroke (Vmax), action potential duration at 30%, 50% and 90% repolarization (APD30, APD50 and APD90), before (control) and after administration and washout of A-803467. *p < 0.05 vs. control at 0.5 Hz, **p < 0.01 vs. control at 0.5 Hz, #p < 0.05 vs. control at 0.2 Hz, ##p < 0.01 vs. control at 0.2 Hz (N = 10 and n = 10, respectively).

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  Figure 3. Effect of A-803467 (3–1,000 nmol/L) administration on action potential properties in canine left ventricular Purkinje fibers (N = number of dogs; n = number of tissue slices). (A–F) Average data for action potential amplitude (APA), maximum diastolic potential (MDP), maximum rate of rise of the action potential upstroke (Vmax), action potential duration at 30%, 50% and 90% repolarization (APD30, APD50 and APD90), before (control) and after administration and washout of A-803467. *p < 0.05 vs. control at 0.5 Hz, **p < 0.01 vs. control at 0.5 Hz, #p < 0.05 vs. control at 0.2 Hz, ##p < 0.01 vs. control at 0.2 Hz (N = 6 and n = 6, respectively).

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  Figure 4. A-803467 inhibits early afterdepolarizations (EADs) and Nav1.8 induced INa,L in Purkinje fibers and cells (N = number of dogs; n = number of tissue slices or cells). (A) The incidence of EADs in Purkinje fibers exposed to ATX-II (10 nmol/L) alone or in combination with 100 nmol/L A-803467. The inset shows an example of A-803467 suppressing the EAD elicited by exposure to ATX-II at 0.5 Hz. *p < 0.05 vs. control + ATX (N = 8 and n = 8, respectively). (B) 100 nmol/L A-803467 inhibits SCN10A-mediated INa,L in transfected ND7/23 cells. (C) Summary data of relative INa,L at −20 mV in the absence (control) and presence of 100 nmol/L A-803467 in Purkinje cells. #p < 0.05 vs. control (N = 6 and n = 8, respectively).