Stretch-activated currents in cardiomyocytes isolated from rabbit pulmonary veins

• Published in: Progress in biophysics and molecular biology Vol. 97; no. 2; pp. 217 - 231
• Main Authors: Seol, Chang Ahn, Kim, Won Tae, Ha, Jeong Mi, Choe, Han, Jang, Yeon Jin, Youm, Jae Boum, Earm, Yung E., Leem, Chae Hun
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-06-2008
• Subjects: 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid - pharmacology; Animals; Atrial Fibrillation - physiopathology; Cardiomyocytes in pulmonary veins; Hypotonic challenge; In Vitro Techniques; Ion Channel Gating - drug effects; Ion Channel Gating - physiology; Ion Transport; Ions - metabolism; Mechanical stretch; Mechanical stretch-activated Cl − current; Mechanical stretch-activated nonselective current; Mechanotransduction, Cellular - physiology; Membrane Potentials; Myocytes, Cardiac - physiology; Pulmonary Veins - cytology; Rabbits; Streptomycin - pharmacology; Stress, Mechanical; Swelling-activated Cl − current; Swelling-induced nonselective current; Cardiomyocytes in pulmonary veins; Swelling-induced nonselective current; Mechanical stretch-activated Cl − current; Swelling-activated Cl − current; Mechanical stretch; Mechanical stretch-activated nonselective current; Hypotonic challenge
• ISSN: 0079-6107; 1873-1732
• DOI: 10.1016/j.pbiomolbio.2008.02.008

Evidence is growing of a relationship between atrial dilation and atrial fibrillation (AF), the most prevalent type of arrhythmia. Pulmonary veins, which are important ectopic foci for provoking AF, are of increasing interest in relation to the early development of AF. Here, using single cardiomyocytes isolated from rabbit pulmonary veins, we characterised the stretch-activated currents induced by swelling and axial mechanical stretching. Swelling induced both a stretch-activated nonselective cationic current (NSC) and a Cl
− current. The swelling-induced Cl
− current (
I
Cl,swell) was inhibited by DIDS, whereas the swelling-induced NSC (
I
NSC,swell) was inhibited by Gd
3+. The cationic selectivity of the
I
NSC,swell was K
+>Cs
+>Na
+>Li
+, whilst the P
K/P
Na, P
Cs/P
Na, and P
Li/P
Na permeability ratios were 2.84, 1.86, and 0.85, respectively. Activation of the
I
NSC,swell was faster than that of the
I
Cl,swell. Given a high K
+ concentration in the bath solution, the
I
NSC,swell showed limited amplitude (<−70
mV). Mechanical stretching induced an immediate Gd
3+- and streptomycin-sensitive NSC (
I
NSC,stretch) that was permeable to Na
+, K
+, Cs
+ and NMDG. Persistent stretching activated a DIDS-sensitive current (
I
Cl,stretch). The
I
NSC,stretch, but not the
I
NSC,swell, was completely blocked by 400
μM streptomycin; therefore, the two currents may not be associated with the same channel. In addition, the type of current induced may depend on the type of stretching. Thus, stretch-induced anionic and cationic currents are functionally present in the cardiomyocytes of the main pulmonary veins of rabbits, and they may have pathophysiological roles in the development of AF under stretched conditions.