Fig 1.
Action potential duration (APD90) and resting membrane potential in WT and CVB3+ cardiomyocytes.
(A) Recordings of cellular action potentials from WT and CVB3+ cardiomyocytes. Action potential duration was unaltered between both genotypes. mV = millivolt, ms = milliseconds. (B) APD90 in WT and CVB3+ cardiomyocytes at 1 Hz stimulation. WT n = 7; CVB3+ n = 14. n = number of cardiomyocytes. (C) APD90 in WT and CVB3+ cardiomyocytes at 2 Hz stimulation. WT n = 7; CVB3+ n = 14. (D) APD90 in WT and CVB3+ cardiomyocytes at 5 Hz stimulation. WT n = 7; CVB3+ n = 14. (E) Resting membrane potential in WT and CVB3+ cardiomyocytes at 1 Hz. WT n = 7; CVB3+ n = 14; *p<0.005. (F) Resting membrane potential in WT and CVB3+ cardiomyocytes at 2 Hz. WT n = 7; CVB3+ n = 14; *p<0.005. (G) Resting membrane potential in WT and CVB3+ cardiomyocytes at 5 Hz. WT n = 6; CVB3+ n = 14; *p<0.005.
Fig 2.
Early afterdepolarizations (EADs) in WT and CVB3 cardiomyocytes.
(A) Representative trace of cellular action potentials and EADs in a WT cardiomyocyte. mV = millivolt, ms = milliseconds. (B) Representative trace of cellular action potentials and EADs in a CVB3+ cardiomyocyte. (C) Mean occurrence of EADs in WT and CVB3+ cardiomyocytes at 1,2 and 5 Hz. WT n = 4; CVB3+ n = 10. n = number of cardiomyocytes. (D) Mean amplitude of EADs in WT and CVB3+ cardiomyocytes. WT n = 4; CVB3+ n = 10.
Fig 3.
Monophasic action potentials and action potential duration (APD90) in WT and CVB3+ whole hearts.
(A) Representative recording of monophasic action potentials in a Langendorff-perfused WT whole heart at pacing with S1 = 100 ms (ms = milliseconds). mV = millivolt, s = seconds. ↓ = electrical stimulus artefact. (B) Representative recording of monophasic action potentials in a Langendorff-perfused CVB3+ whole heart at pacing with S1 = 100 ms. (C) APD90 in Langendorff-perfused WT and CVB3+ hearts at pacing with S1 = 100 ms. WT n = 7; CVB3+ n = 7. n = number of Langendorff-perfused hearts. (D) APD90 in Langendorff-perfused WT and CVB3+ hearts at pacing with S1 = 120 ms. WT n = 7; CVB3+ n = 7. (E) APD90 in Langendorff-perfused WT and CVB3+ hearts at pacing with S1 = 150 ms. WT n = 6; CVB3+ n = 7. Within each genotype, we found a heart rate dependent shortening of ADP90 with increasing heart rate. (WT ADP90 at: S1 = 100 ms vs. S1 = 150 ms, p = 0.014; CVB3+ ADP90 at: S1 = 100 ms vs. S1 = 150 ms, p = 0.001).
Fig 4.
Ventricular effective refractory period (VERP) in WT and CVB3+ whole hearts.
(A) Recording of S1S2 electrical stimulation protocol in a Langendorff-perfused WT whole heart. ↓ = S1 electrical stimulus artefact. S1 cycle length was 120 ms (ms = milliseconds). Δ = S2 extra-stimulus for determination of VERP. In this example, S2 had a coupling interval of 46 ms that caused a subsequent ventricular depolarization. # = first intrinsic ventricular action potential. mV = millivolt, s = second. (B) Recording of S1S2 electrical stimulation protocol in a Langendorff-perfused CVB3+ whole heart. S2 extra-stimulus (Δ) coupling interval was also 46 ms that did not cause a subsequent ventricular depolarization, indicating ventricular refractoriness (VERP). (C) VERP in Langendorff-perfused WT and CVB3+ whole hearts. WT n = 5; CVB3+ n = 7; *p = 0.018. n = number of Langendorff-perfused hearts.
Fig 5.
Resting heart rate in WT and CVB3+ whole hearts.
(A) Representative recording of resting heart rate in a Langendorff-perfused WT whole heart. mV = millivolt, s = seconds, P = P wave, QRS = QRS complex. Heart rate is 382 bpm (bpm = beats per minute). (B) Representative recording of resting heart rate in a Langendorff-perfused CVB3+ whole heart. Heart rate is 347 bpm. (C) Mean resting heart rate in Langendorff-perfused WT and CVB3+ whole hearts. WT n = 7; CVB3+ n = 7. n = number of Langendorff-perfused hearts.