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


RESULTS
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.


CONCLUSIONS
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.
Research Center, Montreal Heart Institute, Université de Montréal, Quebec, Canada.
Scott A
SA
Grandy
Judith
J
Brouillette
Céline
C
Fiset
D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D015536:Down-Regulation; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000276:immunology / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000235:genetics*; D006352:Heart Ventricles / Q000378:metabolism / Q000503:physiopathology; D018836:Inflammation Mediators / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D051379:Mice; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000378:metabolism*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015415:Biomarkers; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D062554:NAV1.5 Voltage-Gated Sodium Channel; D012333:RNA, Messenger; C568321:Scn5a protein, mouse; D015222:Sodium Channels; D014409:Tumor Necrosis Factor-alpha; D012964:Sodium