Abstract：
BACKGROUND:Several mammalian species display distinct biophysical properties between atrial and ventricular voltage-gated sodium current (INa); however, the potential mechanism behind this phenomenon is unknown. OBJECTIVE:The purpose of this study was to investigate the potential molecular identities of the different INa in atrial and ventricular myocytes of rat hearts. METHODS:Whole-cell patch voltage-clamp and molecular biology techniques were used in the study. RESULTS:Ventricular INa exhibited a slower inactivation, more positive potential of inactivation, and quicker recovery from inactivation compared to atrial INa. Real-time polymerase chain reaction and western blot analysis revealed that mRNA and protein levels of NaVβ2 and NaVβ4 subunits, but not NaV1.5, were greater in ventricular myocytes than in atrial myocytes. INa in heterologous HEK 293 cell expression system with coexpressing hNaV1.5 and hNaVβ2/hNaVβ4 showed similar biophysical properties to ventricular INa. Greater protein expression of NaVβ2 and NaVβ4 subunits was also observed in human ventricles. Interestingly, pharmacologic study revealed that the antiarrhythmic drug dronedarone (10 μM) inhibited atrial INa more (by 73%) than ventricular INa (by 42%), and shifted its inactivation to more negative voltages (-4.6 mV) compared to ventricular INa. CONCLUSION:The results of this study demonstrate the novel information that the distinctive biophysical properties of INa in atrial and ventricular myocytes can be attributed to inhomogeneous expression of NaVβ2 and NaVβ4 subunits, and that atrial INa is more sensitive to inhibition by dronedarone.
journal_name
Heart Rhythmjournal_title
Heart rhythmauthors
Chen KH,Xu XH,Sun HY,Du XL,Liu H,Yang L,Xiao GS,Wang Y,Jin MW,Li GRdoi
10.1016/j.hrthm.2015.11.022subject
Has Abstractpub_date
2016-03-01 00:00:00pages
762-70issue
3eissn
1547-5271issn
1556-3871pii
S1547-5271(15)01429-0journal_volume
13pub_type
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