A variety of K channels regulate he action potential in cardiac cells. The HERG channel is unusual in that its primary structure resembles that of many depolarization-activated channels, such as Shaker, whereas functionally it displays properties of the inward rectifier. The inward rectification, however, seems to derive from intrinsic gating properties, rather than the more common blockade mechanism. The proposed research will analyze the gating of exogenously expressed human HERG channels, and the effects of channel blockers.
The specific aims are to elucidate the biophysical and molecular mechanisms that account for the voltage-dependent behavior of HERG and to examine the mechanisms of interaction with various pharmacological inhibitors.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
7R01HL057383-03
Application #
2794258
Study Section
Physiology Study Section (PHY)
Project Start
1997-01-25
Project End
2000-12-31
Budget Start
1998-05-01
Budget End
1998-12-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Harvard University
Department
Biology
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
Smith, Paula L; Yellen, Gary (2002) Fast and slow voltage sensor movements in HERG potassium channels. J Gen Physiol 119:275-93
Rothberg, Brad S; Shin, Ki Soon; Phale, Prashant S et al. (2002) Voltage-controlled gating at the intracellular entrance to a hyperpolarization-activated cation channel. J Gen Physiol 119:83-91
Shin, K S; Rothberg, B S; Yellen, G (2001) Blocker state dependence and trapping in hyperpolarization-activated cation channels: evidence for an intracellular activation gate. J Gen Physiol 117:91-101
Yellen, G (1999) The bacterial K+ channel structure and its implications for neuronal channels. Curr Opin Neurobiol 9:267-73
Yellen, G (1998) The moving parts of voltage-gated ion channels. Q Rev Biophys 31:239-95