Reduction of ventricular sodium current in a mouse model of HIV

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 (I(Na)) in a transgenic model of HIV (CD4C/HIV mice), which exhibit a severe AIDS-like disease.

Patch-clamp techniques were used to examine I(Na) and action potentials (AP) in ventricular myocytes isolated from HIV and wild-type (WT) mice. In HIV myocytes peak I(Na) 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 I(Na) 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 (V(max); 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-1beta 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.

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.