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Vol. 62, Issue 6, 1456-1463, December 2002
1.3 Subunit Modulates Drug Block of hKv1.5
Channels
Institute of Pharmacology and Toxicology (Consejo Superior de
Investigaciones Cientificas), School of Medicine, Universidad
Complutense, Madrid, Spain (T.G., C.A., R.C., I.M., E.D., J.T., C.V.)
and Department of Physiology, Colorado State University, Fort Collins,
Colorado (R.N.-P., M.M.T.)
The assembly of voltage-gated potassium (Kv) channels with 
subunits
modifies the electrophysiological characteristics of the 
subunits.
Kv1.3 subunits shift the midpoint of the activation curve toward
more negative voltages and slow the deactivation process. In addition,
the Kv1.3 subunit converts hKv1.5 from a delayed rectifier with a
modest degree of slow inactivation to a channel with both fast and slow
components of inactivation. In the present study, we have analyzed the
effects of bupivacaine and a permanently charged analog
[R(+)-N-methyl-bupivacaine
(RB+1C)] on Kv1.5 and Kv1.5+Kv1.3 channels
expressed in human embryonic kidney 293 cells using the whole-cell
configuration of the patch-clamp technique. Block induced by
RB+1C binding to its external receptor site was not
modified by the presence of this subunit. However,
hKv1.5+Kv1.3 channels were ~4-fold less sensitive to
bupivacaine than hKv1.5 channels in the absence of subunits
(IC50 = 47.5 ± 5.1 versus 13.1 ± 0.8 µM,
respectively, p < 0.01). Quinidine was also less
potent to block Kv1.5+Kv1.3 channels than Kv1.5 channels
(IC50 = 49.6 µM versus 6.2 µM, respectively).
These results suggest that the Kv1.3 subunit does not modify the
affinity of the charged bupivacaine for its external receptor site but
markedly reduces the affinity of bupivacaine and quinidine for their
internal receptor site in hKv1.5 channels.
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