Format

Send to

Choose Destination
See comment in PubMed Commons below
Biophys J. 2011 Aug 3;101(3):631-42. doi: 10.1016/j.bpj.2011.06.050.

Models of HERG gating.

Author information

1
Center for Cellular and Systems Electrophysiology, Gynecology-Obstetrics, State University of New York, University at Buffalo, Buffalo, New York, USA. bett@buffalo.edu

Abstract

HERG (Kv11.1, KCNH2) is a voltage-gated potassium channel with unique gating characteristics. HERG has fast voltage-dependent inactivation, relatively slow deactivation, and fast recovery from inactivation. This combination of gating kinetics makes study of HERG difficult without using mathematical models. Several HERG models have been developed, with fundamentally different organization. HERG is the molecular basis of I(Kr), which plays a critical role in repolarization. We programmed and compared five distinct HERG models. HERG gating cannot be adequately replicated using Hodgkin-Huxley type formulation. Using Markov models, a five-state model is required with three closed, one open, and one inactivated state, and a voltage-independent step between some of the closed states. A fundamental difference between models is the presence/absence of a transition directly from the proximal closed state to the inactivated state. The only models that effectively reproduce HERG data have no direct closed-inactivated transition, or have a closed-inactivated transition that is effectively zero compared to the closed-open transition, rendering the closed-inactivation transition superfluous. Our single-channel model demonstrates that channels can inactivate without conducting with a flickering or bursting open-state. The various models have qualitative and quantitative differences that are critical to accurate predictions of HERG behavior during repolarization, tachycardia, and premature depolarizations.

PMID:
21806931
PMCID:
PMC3145286
DOI:
10.1016/j.bpj.2011.06.050
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science Icon for PubMed Central
    Loading ...
    Support Center