Referenced in: none

Automatically associated channels: Kv1.5 , Slo1

Title: Direct block of cloned hKv1.5 channel by cytochalasins, actin-disrupting agents.

Authors: Bok Hee Choi, Jung-Ah Park, Kyung-Ryoul Kim, Ggot-Im Lee, Yong-Tae Lee, Huhn Choe, Seong-Hoon Ko, Min-Ho Kim, Yeon-Ho Seo, Yong-Geun Kwak

Journal, date & volume: Am. J. Physiol., Cell Physiol., 2005 Aug , 289, C425-36

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15800051

Abstract
The action of cytochalasins, actin-disrupting agents on human Kv1.5 channel (hKv1.5) stably expressed in Ltk(-) cells was investigated using the whole cell patch-clamp technique. Cytochalasin B inhibited hKv1.5 currents rapidly and reversibly at +60 mV in a concentration-dependent manner with an IC(50) of 4.2 microM. Cytochalasin A, which has a structure very similar to cytochalasin B, inhibited hKv1.5 (IC(50) of 1.4 microM at +60 mV). Pretreatment with other actin filament disruptors cytochalasin D and cytochalasin J, and an actin filament stabilizing agent phalloidin had no effect on the cytochalasin B-induced inhibition of hKv1.5 currents. Cytochalasin B accelerated the decay rate of inactivation for the hKv1.5 currents. Cytochalasin B-induced inhibition of the hKv1.5 channels was voltage dependent with a steep increase over the voltage range of the channel's opening. However, the inhibition exhibited voltage independence over the voltage range in which channels are fully activated. Cytochalasin B produced no significant effect on the steady-state activation or inactivation curves. The rate constants for association and dissociation of cytochalasin B were 3.7 microM/s and 7.5 s(-1), respectively. Cytochalasin B produced a use-dependent inhibition of hKv1.5 current that was consistent with the slow recovery from inactivation in the presence of the drug. Cytochalasin B (10 microM) also inhibited an ultrarapid delayed rectifier K(+) current (I(K,ur)) in human atrial myocytes. These results indicate that cytochalasin B primarily blocks activated hKv1.5 channels and endogenous I(K,ur) in a cytoskeleton-independent manner as an open-channel blocker.