Role of sarcolemmal BK(Ca) channels in stretch-induced extrasystoles in isolated chick hearts.

BACKGROUND It remains unclear whether sarcolemmal BK(Ca) channels in post-hatch chick ventricular myocytes contribute to stretch-induced extrasystoles (SIE), and whether they are stretch-activated BK(Ca) (SAK(Ca)) channels or a non-stretch-sensitive BK(Ca) variant. METHODS AND RESULTS To determine the role of sarcolemmal BK(Ca) channels in SIE and their stretch sensitivity, an isolated 2-week-old Langendorff-perfused chick heart and mathematical simulation were used. The ventricular wall was rapidly stretched by application of a volume change pulse. As the speed of the stretch increased, the probability of SIE also significantly increased, significantly shortening the delay between SIE and the initiation of the stretch. Application of 100 nmol/L of Grammostola spatulata mechanotoxin 4, a cation-selective stretch-activated channel (SAC) blocker, significantly decreased the probability of SIE. The application of Iberiotoxin, however, a BK(Ca) channel blocker, significantly increased the probability of SIE, suggesting that a K(+) efflux via a sarcolemmal BK(Ca) channel reduces SIE by balancing out stretch-induced cation influx via SACs. The simulation using a cardiomyocyte model combined with a new stretch sensitivity model that considers viscoelastic intracellular force transmission showed that stretch sensitivity in BK(Ca) channels is required to reproduce the present wet experimental results. CONCLUSIONS Sarcolemmal BK(Ca) channels in post-hatch chick ventricular myocytes are SAK(Ca) channels, and they have a suppressive effect on SIE.

[1]  G. Grover,et al.  The cardioprotective, vasorelaxant and electrophysiological profile of the large conductance calcium-activated potassium channel opener NS-004. , 1993, The Journal of pharmacology and experimental therapeutics.

[2]  P. Hunter,et al.  Stretch-induced changes in heart rate and rhythm: clinical observations, experiments and mathematical models. , 1999, Progress in biophysics and molecular biology.

[3]  Peter Kohl,et al.  Force-length relations in isolated intact cardiomyocytes subjected to dynamic changes in mechanical load. , 2007, American journal of physiology. Heart and circulatory physiology.

[4]  Raimond L Winslow,et al.  Comparison of putative cooperative mechanisms in cardiac muscle: length dependence and dynamic responses. , 1999, American journal of physiology. Heart and circulatory physiology.

[5]  U G Hofmann,et al.  Investigating the cytoskeleton of chicken cardiocytes with the atomic force microscope. , 1997, Journal of structural biology.

[6]  D. Allen,et al.  The effects of muscle length on intracellular calcium transients in mammalian cardiac muscle. , 1982, The Journal of physiology.

[7]  P Kohl,et al.  Cellular mechanisms of cardiac mechano-electric feedback in a mathematical model. , 1998, The Canadian journal of cardiology.

[8]  K. Naruse,et al.  Characterization of a newly found stretch-activated KCa,ATP channel in cultured chick ventricular myocytes. , 1999, American journal of physiology. Heart and circulatory physiology.

[9]  M. Shoda,et al.  Stretch‐activated anion currents of rabbit cardiac myocytes. , 1992, The Journal of physiology.

[10]  Kimihide Hayakawa,et al.  Actin stress fibers transmit and focus force to activate mechanosensitive channels , 2008, Journal of Cell Science.

[11]  Satoshi Nishimura,et al.  Membrane potential of rat ventricular myocytes responds to axial stretch in phase, amplitude and speed-dependent manners. , 2006, Cardiovascular research.

[12]  G. Iribe,et al.  Effects of axial stretch on sarcolemmal BKCa channels in post‐hatch chick ventricular myocytes , 2010, Experimental physiology.

[13]  Kimiko Yamamoto,et al.  Vascular mechanobiology: endothelial cell responses to fluid shear stress. , 2009, Circulation journal : official journal of the Japanese Circulation Society.

[14]  D. Noble,et al.  The Role of Sodium ‐ Calcium Exchange during the Cardiac Action Potential a , 1991, Annals of the New York Academy of Sciences.

[15]  Rebecca A. B. Burton,et al.  Axial Stretch of Rat Single Ventricular Cardiomyocytes Causes an Acute and Transient Increase in Ca2+ Spark Rate , 2009, Circulation research.

[16]  Hiroyuki Watanabe,et al.  Molecular and Electrical Remodeling of L- and T-Type Ca2+ Channels in Rat Right Atrium With Monocrotaline-Induced Pulmonary Hypertension , 2009 .

[17]  P. Kohl,et al.  Axial stretch enhances sarcoplasmic reticulum Ca2+ leak and cellular Ca2+ reuptake in guinea pig ventricular myocytes: experiments and models. , 2008, Progress in biophysics and molecular biology.

[18]  D. Noble,et al.  Improved guinea-pig ventricular cell model incorporating a diadic space, IKr and IKs, and length- and tension-dependent processes. , 1998, The Canadian journal of cardiology.

[19]  K. Naruse,et al.  Stress-Axis Regulated Exon (STREX) in the C terminus of BK(Ca) channels is responsible for the stretch sensitivity. , 2009, Biochemical and biophysical research communications.

[20]  M J Lab,et al.  Mechano-electric feedback. , 1996, Cardiovascular research.

[21]  R Latorre,et al.  Gating kinetics of Ca2+-activated K+ channels from rat muscle incorporated into planar lipid bilayers. Evidence for two voltage- dependent Ca2+ binding reactions , 1983, The Journal of general physiology.

[22]  Eric Mazur,et al.  Viscoelastic retraction of single living stress fibers and its impact on cell shape, cytoskeletal organization, and extracellular matrix mechanics. , 2006, Biophysical journal.

[23]  Masahiro Sokabe,et al.  Tuning the mechanosensitivity of a BK channel by changing the linker length , 2008, Cell Research.

[24]  F. Sachs,et al.  Tarantula peptide inhibits atrial fibrillation , 2001, Nature.

[25]  F Sachs,et al.  Stretch-activated ion channels in tissue-cultured chick heart. , 1993, The American journal of physiology.

[26]  K. Jacobson,et al.  Local measurements of viscoelastic parameters of adherent cell surfaces by magnetic bead microrheometry. , 1998, Biophysical journal.

[27]  D E Hansen,et al.  Dose-dependent inhibition of stretch-induced arrhythmias by gadolinium in isolated canine ventricles. Evidence for a unique mode of antiarrhythmic action. , 1991, Circulation research.

[28]  E. White,et al.  Activation of Na+–H+ exchange and stretch‐activated channels underlies the slow inotropic response to stretch in myocytes and muscle from the rat heart , 2004, The Journal of physiology.

[29]  Peter Kohl,et al.  Extracorporeal cardiac mechanical stimulation: precordial thump and precordial percussion. , 2010, British medical bulletin.