Referenced in: none

Automatically associated channels: Kv1.5 , Slo1

Title: Assembly with the Kvbeta1.3 subunit modulates drug block of hKv1.5 channels.

Authors: Teresa Gonzalez, Ricardo Navarro-Polanco, Cristina Arias, Ricardo Caballero, Ignacio Moreno, Eva Delpón, Juan Tamargo, Michael M Tamkun, Carmen Valenzuela

Journal, date & volume: Mol. Pharmacol., 2002 Dec , 62, 1456-63

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/12435814

Abstract
The assembly of voltage-gated potassium (Kv) channels with beta subunits modifies the electrophysiological characteristics of the alpha subunits. Kvbeta1.3 subunits shift the midpoint of the activation curve toward more negative voltages and slow the deactivation process. In addition, the Kvbeta1.3 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 Kvalpha1.5 and Kvalpha1.5+Kvbeta1.3 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 beta subunit. However, hKvalpha1.5+Kvbeta1.3 channels were ~4-fold less sensitive to bupivacaine than hKv1.5 channels in the absence of beta subunits (IC(50) = 47.5 +/- 5.1 versus 13.1 +/- 0.8 microM, respectively, p < 0.01). Quinidine was also less potent to block Kvalpha1.5+Kvbeta1.3 channels than Kvalpha1.5 channels (IC(50) = 49.6 microM versus 6.2 microM, respectively). These results suggest that the Kvbeta1.3 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.