Selected contribution: axial stretch increases spontaneous pacemaker activity in rabbit isolated sinoatrial node cells.

Isolated, spontaneously beating rabbit sinoatrial node cells were subjected to longitudinal stretch, using carbon fibers attached to both ends of the cell. Their electrical behavior was studied simultaneously in current-clamp or voltage-clamp mode using the perforated patch configuration. Moderate stretch ( approximately 7%) caused an increase in spontaneous beating rate (by approximately 5%) and a reduction in maximum diastolic and systolic potentials (by approximately 2.5%), as seen in multicellular preparations. Mathematical modeling of the stretch intervention showed the experimental results to be compatible with stretch activation of cation nonselective ion channels, similar to those found in other cardiac cell populations. Voltage-clamp experiments validated the presence of a stretch-induced current component with a reversal potential near -11 mV. These data confirm, for the first time, that the positive chronotropic response of the heart to stretch is, at least in part, encoded on the level of individual sinoatrial node pacemaker cells; all reported data are in agreement with a major contribution of stretch-activated cation nonselective channels to this response.

[1]  W Craelius,et al.  Stretch‐activation of rat cardiac myocytes , 1993, Experimental physiology.

[2]  P Kohl,et al.  Mechanosensitive connective tissue: potential influence on heart rhythm. , 1996, Cardiovascular research.

[3]  S. Hosoda,et al.  Enhancement of the L-type Ca2+ current by mechanical stimulation in single rabbit cardiac myocytes. , 1996, Circulation research.

[4]  G. Bett,et al.  Stretch-activated whole cell currents in adult rat cardiac myocytes. , 2000, American journal of physiology. Heart and circulatory physiology.

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

[6]  F. Sachs,et al.  Activation and Inactivation of Mechanosensitive Currents in the Chick Heart , 2000, The Journal of Membrane Biology.

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

[8]  C. Baumgarten,et al.  Swelling-activated Gd3+-sensitive Cation Current and Cell Volume Regulation in Rabbit Ventricular Myocytes , 1997, The Journal of general physiology.

[9]  F A Bainbridge,et al.  The influence of venous filling upon the rate of the heart , 1915, The Journal of physiology.

[10]  D DiFrancesco,et al.  Modulation of single hyperpolarization‐activated channels (i(f)) by cAMP in the rabbit sino‐atrial node. , 1994, The Journal of physiology.

[11]  E. White,et al.  Cyclic AMP but not phosphorylation of phospholamban contributes to the slow inotropic response to stretch in ferret papillary muscle , 1999, Pflügers Archiv.

[12]  J. Le Guennec,et al.  A new method of attachment of isolated mammalian ventricular myocytes for tension recording: length dependence of passive and active tension. , 1990, Journal of molecular and cellular cardiology.

[13]  J R BLINKS,et al.  Positive chronotropic effect of increasing right atrial pressure in the isolated mammalian heart. , 1956, The American journal of physiology.

[14]  M. Lieberman,et al.  Chloride conductance is activated by membrane distention of cultured chick heart cells. , 1996, Cardiovascular research.

[15]  M Lei,et al.  Swelling-induced decrease in spontaneous pacemaker activity of rabbit isolated sino-atrial node cells. , 1998, Acta physiologica Scandinavica.

[16]  M R Boyett,et al.  Correlation between electrical activity and the size of rabbit sino‐atrial node cells. , 1993, The Journal of physiology.

[17]  H. Sugi,et al.  Length-dependent changes of pacemaker frequency in the isolated rabbit sinoatrial node. , 1984, The Japanese journal of physiology.

[18]  C. Brooks,et al.  Effect of stretch on the isolated cat sinoatrial node. , 1966, The American journal of physiology.

[19]  F. Sachs,et al.  Identification of a Peptide Toxin from Grammostola spatulata Spider Venom That Blocks Cation-Selective Stretch-Activated Channels , 2000, The Journal of general physiology.

[20]  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.

[21]  W. Sessa,et al.  Cyclic strain upregulates nitric oxide synthase in cultured bovine aortic endothelial cells. , 1995, The Journal of clinical investigation.

[22]  F Sachs,et al.  Stretch-activated ion channels in the heart. , 1997, Journal of molecular and cellular cardiology.

[23]  William Craelius,et al.  Stretch activated ion channels in ventricular myocytes , 1988, Bioscience reports.