Reduction of ventricular sodium current in a mouse model of HIV.

Effect of HIV on Cardiac Sodium Current. Introduction: Cardiac arrhythmias have been reported in AIDS patients. Arrhythmias can arise from alterations in ventricular Na+ channel function. However, it is unknown whether HIV affects cardiac Na+ channel function. Therefore, the purpose of this study was to characterize the effect of HIV on ventricular Na+ current (INa) in a transgenic model of HIV (CD4C/HIV mice), which exhibit a severe AIDS-like disease. Methods and Results: Patch-clamp techniques were used to examine INa and action potentials (AP) in ventricular myocytes isolated from HIV and wild-type (WT) mice. In HIV myocytes peak INa was reduced (at −50 mV: HIV, −55.3 ± 4.3 pA/pF, n = 15; WT, −79.4 ± 5.2 pA/pF, n = 16, P < 0.05), whereas late INa was similar in both groups (HIV, −4.3 ± 0.4 pA/pF; WT, −4.4 ± 0.4 pA/pF, n = 22/group). AP amplitude (HIV 91.5 ± 4.7 mV, n = 12; WT 104.4 ± 3.1 mV, n = 15, P < 0.05) and the maximal velocity of the AP upstroke (Vmax; HIV, 57.2 ± 9.3 mV/ms, n = 12; WT, 113.5 ± 8 mV/ms, n = 15, P < 0.05) were decreased in HIV myocytes. ECG recordings revealed that the QRS complex was prolonged in HIV mice (HIV, 15.7 ± 0.2 ms, n = 22; WT, 14.1 ± 0.5 ms, n = 10, P < 0.05). The serum levels of interleukin-1β were elevated in HIV mice (HIV, 18.1 ± 3.1 pg/mL, n = 3; WT, 5.1 ± 1.1 pg/mL, n = 4, P < 0.05) in line with previous evidence that suggests that elevated levels of cytokines can affect cardiac ion currents. Conclusion: Overall, our observations suggest that elevated levels of proinflammatory cytokines in CD4C/HIV mice could alter Na+ channel function, thus altering cardiac depolarization and contribute to the generation of arrhythmias. (J Cardiovasc Electrophysiol, Vol. 21, pp. 916-922, August 2010)