Figure 2.
Electrophysiological comparison between RVCM and LVCM.(A–C) Larger Ito in RVCM. (A) Representative traces of Ito activated by step pulses from −60 to 60 mV (1 s) every 10 s in LVCM (black line) and RVCM (gray line). (B) Density of Ito (amplitude of fast inactivating outward current/membrane capacitance) plotted against the clamp voltage (n = 23 and 21, n = 6, P < 0.0001). (C) Voltage-dependent inactivation curves obtained by a double-pulse protocol (inset) and fitted to the Boltzmann equation. The peak current elicited by the common test pulse (30 mV) was normalized to the maximum value and plotted as a function of the conditioning voltages (−90 to −20 mV). The half-maximum inactivation voltage (V1/2,inact) did not differ between RVCM and LVCM. (D–F) VOCCL current (ICa,L) and AP-induced Ca2+ influx. (D) Representative traces of ICa,L recorded under the nystatin-perforated patch clamp using CsCl pipette solution. ICa,L was activated by repetitive step pulses from −30 to 50 mV (300 ms) every 10 s. The presented traces are nifedipine-sensitive currents in LVCM (black line) and RVCM (gray line). (E) The peak amplitudes of the nifedipine-sensitive current were normalized to Cm and plotted against the test voltage (n = 22 and 19, n = 6). (F) Steady-state voltage-dependent inactivation of ICa,L was obtained by two-step pulse protocol (inset). The evoked pulse at 10 mV (300 ms) from various conditioning pulses normalized to the maximum value and plotted as a function of the conditioning potential. The G-V relationships were fitted to the Boltzmann function, showing no difference between the two ventricles. We tested the significance of Ito and ICa,L using MANOVA. (G) Mathematical simulation of AP. The calculated APs of the Pandit model (Pandit et al., 2001; dotted line) and the modified results reflecting the measured parameters in LVCM (black solid line) and RVCM (gray line). (H) Summary of the integral of Ca2+ flux evoked by the AP-clamp technique in LVCM and RVCM. The cumulated Ca2+ influx is larger in LVCM (n = 16 and 17, and n = 4). Nested t test was used for testing the significance of Ca2+ influx. **, P < 0.01.

Electrophysiological comparison between RVCM and LVCM. (A–C) Larger Ito in RVCM. (A) Representative traces of Ito activated by step pulses from −60 to 60 mV (1 s) every 10 s in LVCM (black line) and RVCM (gray line). (B) Density of Ito (amplitude of fast inactivating outward current/membrane capacitance) plotted against the clamp voltage (n = 23 and 21, n = 6, P < 0.0001). (C) Voltage-dependent inactivation curves obtained by a double-pulse protocol (inset) and fitted to the Boltzmann equation. The peak current elicited by the common test pulse (30 mV) was normalized to the maximum value and plotted as a function of the conditioning voltages (−90 to −20 mV). The half-maximum inactivation voltage (V1/2,inact) did not differ between RVCM and LVCM. (D–F) VOCCL current (ICa,L) and AP-induced Ca2+ influx. (D) Representative traces of ICa,L recorded under the nystatin-perforated patch clamp using CsCl pipette solution. ICa,L was activated by repetitive step pulses from −30 to 50 mV (300 ms) every 10 s. The presented traces are nifedipine-sensitive currents in LVCM (black line) and RVCM (gray line). (E) The peak amplitudes of the nifedipine-sensitive current were normalized to Cm and plotted against the test voltage (n = 22 and 19, n = 6). (F) Steady-state voltage-dependent inactivation of ICa,L was obtained by two-step pulse protocol (inset). The evoked pulse at 10 mV (300 ms) from various conditioning pulses normalized to the maximum value and plotted as a function of the conditioning potential. The G-V relationships were fitted to the Boltzmann function, showing no difference between the two ventricles. We tested the significance of Ito and ICa,L using MANOVA. (G) Mathematical simulation of AP. The calculated APs of the Pandit model (Pandit et al., 2001; dotted line) and the modified results reflecting the measured parameters in LVCM (black solid line) and RVCM (gray line). (H) Summary of the integral of Ca2+ flux evoked by the AP-clamp technique in LVCM and RVCM. The cumulated Ca2+ influx is larger in LVCM (n = 16 and 17, and n = 4). Nested t test was used for testing the significance of Ca2+ influx. **, P < 0.01.

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