Atrial fibrillation (AF) is the most common sustained arrhythmia clinically. There are accumulating evidence to suggest that ion channel modulation and remodeling play a significant role in the maintenance of AF. A variety of ionic channel abnormalities have been reported in atrial myocytes from patients and animal models with AF. Importantly, a decrease in Ca2+ current density by ~70% in atrial myocytes of patients with persistent AF has been reported. We have obtained recent evidence to demonstrate that several isoforms of small conductance Ca2+- activated K+ channels (SK or KCa2 channels) are expressed and play important roles in the repolarization of human atrial myocytes. Moreover, we have obtained new evidence to support the functional crosstalk between Ca2+ and SK channels. Hence, the goal of the proposal is test the functional coupling between SK and Cav1.3 channels at multiple levels in three independent yet mechanistically linked Aims. The critical roles of these subclasses of KCa channels in human atrial myocytes are only beginning to emerge. Very little is known regarding the regulations of SK channels in the heart. Moreover, mechanistic data from human heart remains extremely limited. Indeed, novel insights into atrial-specific ion channels may provide new treatment paradigms to target these channels without interfering with the excitability of ventricular tissues.
Atrial fibrillation (AF) is the most common sustained arrhythmia clinically. The essence of this proposal is to deploy innovative biochemical, molecular, imaging and functional analyses to test the functional interaction between Ca2+ and SK channels in human atrial myocytes. Novel insights into atrial-specific ion channels may provide new treatment paradigms to target these channels without interfering with the excitability of ventricular tissues.
|Zhang, Xiao-Dong; Timofeyev, Valeriy; Li, Ning et al. (2014) Critical roles of a small conductance Caýýýýý-activated Kýýý channel (SK3) in the repolarization process of atrial myocytes. Cardiovasc Res 101:317-25|
|Rafizadeh, Sassan; Zhang, Zheng; Woltz, Ryan L et al. (2014) Functional interaction with filamin A and intracellular Ca2+ enhance the surface membrane expression of a small-conductance Ca2+-activated K+ (SK2) channel. Proc Natl Acad Sci U S A 111:9989-94|
|Wang, Wenying; Kim, Hyo Jeong; Lee, Jeong-Han et al. (2014) Functional significance of K+ channel ?-subunit KCNE3 in auditory neurons. J Biol Chem 289:16802-13|
|Despa, Sanda; Sharma, Savita; Harris, Todd R et al. (2014) Cardioprotection by controlling hyperamylinemia in a "humanized" diabetic rat model. J Am Heart Assoc 3:|
|Lv, Ping; Kim, Hyo Jeong; Lee, Jeong-Han et al. (2014) Genetic, cellular, and functional evidence for Ca2+ inflow through Cav1.2 and Cav1.3 channels in murine spiral ganglion neurons. J Neurosci 34:7383-93|
|Jian, Zhong; Han, Huilan; Zhang, Tieqiao et al. (2014) Mechanochemotransduction during cardiomyocyte contraction is mediated by localized nitric oxide signaling. Sci Signal 7:ra27|
|Sirish, Padmini; Li, Ning; Liu, Jun-Yan et al. (2013) Unique mechanistic insights into the beneficial effects of soluble epoxide hydrolase inhibitors in the prevention of cardiac fibrosis. Proc Natl Acad Sci U S A 110:5618-23|
|Ulu, Arzu; Harris, Todd R; Morisseau, Christophe et al. (2013) Anti-inflammatory effects of ?-3 polyunsaturated fatty acids and soluble epoxide hydrolase inhibitors in angiotensin-II-dependent hypertension. J Cardiovasc Pharmacol 62:285-97|
|Lieu, Deborah K; Fu, Ji-Dong; Chiamvimonvat, Nipavan et al. (2013) Mechanism-based facilitated maturation of human pluripotent stem cell-derived cardiomyocytes. Circ Arrhythm Electrophysiol 6:191-201|
|Xu, Dan-yan; Davis, Benjamin B; Wang, Zhen-he et al. (2013) A potent soluble epoxide hydrolase inhibitor, t-AUCB, acts through PPAR? to modulate the function of endothelial progenitor cells from patients with acute myocardial infarction. Int J Cardiol 167:1298-304|
Showing the most recent 10 out of 27 publications