To study the difference in membrane ionic currents between hypertrophied and normal myocytes and to explore the electrical remodeling of hypertrophied myocytes.
Membrane ionic channels were studied in enzymatically dispersed spontaneously hypertensive rats (SHRs) left ventricular myocytes using the whole-cell configuration of patch-clamp technique, with normal Wistar rats ventricular myocytes as controls. We observed depolarizing currents (sodium current, INa; L-type calcium current, L-ICa) and repolarizing currents (inward rectifier potassium current, IK1; delayed rectifier potassium current, IK; transient outward potassium current, Ito) and compared the differences between normal and hypertrophied myocytes.
The heart to body weight ratio of Wistar rats and SHRs was 3.70 +/- 0.29 mg/g and 5.66 +/- 0.46 mg/g, respectively (P < 0.001), and the mean cell membrane capacitances were 189.94 +/- 56.59 pF and 280.68 +/- 67.98 pF, respectively (P < 0.05). These differences suggest that SHRs have heart hypertrophy and hypertrophied myocytes. The amplitude of L-Ica of SHRs (1944 +/- 466.8 pA) was significantly greater than that of Wistar rats (1136 +/- 383.3 pA) (P < 0.001), and the current density was 6.93 +/- 1.71 pA/pF and 6.19 +/- 2.85 pA/pF respectively when normalized to cell capacitance, and the slow inactivation time constant of SHRs was significantly prolonged (56.01 +/- 13.36 ms vs 43.63 +/- 17.89 ms, P < 0.001). The amplitude of INa of SHRs (6132.5 +/- 1162.9 pA) was significantly greater than that of Wistar rats (3613.9 +/- 794.44 pA) (P < 0.001), but there was no difference when normalized to cell capacitance (24.61 +/- 6.72 pA/pF vs 24.95 +/- 6.99 pA/pF). Channel activation and inactivation time constants were also the same. The amplitude of IK of SHRs (3461.5 +/- 1967.10 pA) was greater than that of Wistar rats (2302.4 +/- 893.72 pA) (P < 0.05), but there was no difference when normalized to cell capacitance (12.38 +/- 5.46 pA/pF vs 11.86 +/- 3.59 pA/pF). The inward portion of IK1 of SHRs was significantly lower than that of Wistar rats (11.3 +/- 2.26 pA/pF vs 14.3 +/- 3.00 pA/pF, P < 0.05), but there was no difference in the outward portion (2.360 +/- 0.86 pA/pF vs 2.957 +/- 1.27 pA/pF). The current density of Ito of SHRs (8.21 +/- 6.64 pA/pF) was significantly lower than that of Wistar rats (19.16 +/- 6.17 pA/pF) (P < 0.001), but channel kinetics were similar, suggesting that the reduction of Ito may result from the decrease in channel number.
Membrane ionic current changes of hypertrophied left ventricular myocytes in SHRs include: 1. there was an increase of L-Ica, INa and Ik, but the current density was similar to that in normal myocytes, indicating that channel numbers increase as the myocytes become hypertrophied; 2. Ito was small in hypertrophied ventricular myocytes and its current density was even smaller, indicating that channel numbers decrease as the myocytes enlarge. The former is recognized as a physiologically compensatory change which does not lead to electrophysiological disturbance; the latter is viewed as pathological change, where the reduction of Ito may lead to a repolarizing delay in myocytes, prolongation of the action potential and the occurrence of arrhythmias because of repolarizing heterogeneity. Therefore, the reduction of Ito in hypertrophied myocytes should be recognized as a significant or substantial change of electrical remodeling.