KCNE2 modulates the function of Kv4.3 channel / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To understand the role of KCNE2 in functional regulation of Kv4.3, the major alpha subunit of transient outward current (I(to)) in human heart.</p><p><b>METHODS</b>The cDNAs of Kv4.3 or Kv4.3 plus KCNE2 were transfected into COS-7 cells and 24-36 h after the transfection, the channel proteins were expressed in the surface membrane of the cells and the channel currents were recorded with patch-clamp technique in whole-cell mode.</p><p><b>RESULTS</b>KCNE2 played an important role in modulating the channel function. The recorded current density was decreased in cells co-expressing KCNE2 and Kv4.3 to 152.96-/+33.71 pA/pF (n=16) as compared with Kv4.3-expressing cells with a mean current density of 375.13-/+112.87 pA/pF (n=11). At the recording voltage of 60 mV, KCNE2 increased the time to peak (TTP) of the current. TTP in only Kv4.3-expressing cells was 4.82-/+0.32 ms (n=11), significantly shorter than the TTP of 20.41-/+2.13 ms (n=16) in cells co-expressing Kv4.3 and KCNE2 (P<0.05). In the presence of KCNE2, the voltage-dependent inactivation of Kv4.3 showed a positive shift. The voltage of half maximum inactivation (V(0.5)) was decreased significantly from -53.62-/+1.24 mV (n=8) in Kv4.3 group to -46.58-/+1.6 mV (n=10) in KCNE2 co-expression group (P<0.05). KCNE2 accelerated the recovery of the channel from inactivation, reducing the recovery time constant (tau) from 193.43-/+17.98 ms to 137.71-/+18.29 ms.</p><p><b>CONCLUSION</b>KCNE2 might serve as an important beta subunit and play a role in the regulation of I(to) function in human heart.</p>