Ventricular Sodium Currents Are Altered In CD4C/HIV Mice

Abstract

Cardiac arrhythmias have been reported in HIV patients. Studies have shown that HIV can alter ventricular potassium currents, however, little is known about the effect of HIV on ventricular sodium current (INa) even though changes in INa also can lead to rhythm disturbances. Thus, the objective of this study was to characterize the effect of HIV on ventricular INa in CD4C/HIV mice. These mice exhibit a severe AIDS-like disease. 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 INa was significantly depressed between -60 and -30 mV (at -50 mV: HIV, -55.3±4.3 pA/pF, n=15; WT, -79.4±5.2 pA/pF, n=16). However, 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 was similar in HIV (90.7±5.1 mV, n=11) and WT (99.8±4 mV, n=15) myocytes, but the maximal velocity of the AP upstroke (Vmax) was significantly decreased in HIV myocytes (HIV, 54.2±9.6 mV/ms, n=11; WT, 99.2±10.3 mV/ms, n=15). ECG telemetry recordings revealed that the QRS complex was significantly prolonged in HIV mice (HIV, 15.7±0.2 ms, n=22; WT, 14.1±0.5 ms, n=10). Previous studies have shown that elevated levels of cytokines can affect cardiac ion currents. In CD4C/HIV mice serum levels of TNF-alpha are elevated. The present study showed that serum levels of interleukin-1-beta also were elevated in HIV mice (HIV, 18.1±3.1 pg/ml, n=3; WT, 5.1±1.7 pg/ml, n=4). Overall, this study showed that INa is decreased in HIV ventricular myocytes and that this reduction is likely responsible for the observed prolongation of the QRS complex in HIV mice. These alterations could contribute to the development of cardiac rhythm disturbances.