TY - JOUR T1 - Assembly with the Kvβ1.3 Subunit Modulates Drug Block of hKv1.5 Channels JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1456 LP - 1463 DO - 10.1124/mol.62.6.1456 VL - 62 IS - 6 AU - Teresa González AU - Ricardo Navarro-Polanco AU - Cristina Arias AU - Ricardo Caballero AU - Ignacio Moreno AU - Eva Delpón AU - Juan Tamargo AU - Michael M. Tamkun AU - Carmen Valenzuela Y1 - 2002/12/01 UR - http://molpharm.aspetjournals.org/content/62/6/1456.abstract N2 - The assembly of voltage-gated potassium (Kv) channels with β subunits modifies the electrophysiological characteristics of the α subunits. Kvβ1.3 subunits shift the midpoint of the activation curve toward more negative voltages and slow the deactivation process. In addition, the Kvβ1.3 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 Kvα1.5 and Kvα1.5+Kvβ1.3 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 β subunit. However, hKvα1.5+Kvβ1.3 channels were ∼4-fold less sensitive to bupivacaine than hKv1.5 channels in the absence of β subunits (IC50 = 47.5 ± 5.1 versus 13.1 ± 0.8 μM, respectively, p < 0.01). Quinidine was also less potent to block Kvα1.5+Kvβ1.3 channels than Kvα1.5 channels (IC50 = 49.6 μM versus 6.2 μM, respectively). These results suggest that the Kvβ1.3 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. ER -