title: Stretch-activated currents in ventricular myocytes: amplitude and arrhythmogenic effects increase with hypertrophy.
abstract: BACKGROUND
  Mechanical dilation of the human ventricle is known to induce arrhythmias, the underlying ionic mechanisms, however, remain to be clarified.
  
  
  METHODS
  Ventricular myocytes isolated from human, guinea-pig or rat hearts were stretched between the patch electrode and a glass stylus.
  
  
  RESULTS
  Local stretch prolonged the action potential, depolarized the resting membrane and caused extra systoles. Under voltage-clamp conditions, stretch activated several ionic current components. The most prominent current was a stretch activated current (I(SAC)) through non-selective cation channels. I(SAC) followed a linear voltage-dependence, reversed polarity close to 0 mV and was suppressed by 5 microM Gd(3+). During stretch, I(SAC) became steady within 200 ms. I(SAC) did not inactivate and it completely disappeared upon relaxation. Stretch-sensitivity was evaluated from the slope of I(SAC) versus amplitude of stretch. Stretch sensitivity was 75 pA/microm in myocytes from young (3 month), 143 pA/microm in myocytes from old (15 months), and 306 pA/microm in hypertrophied myocytes from old (15 months) spontaneously hypertensive animals. Stretch sensitivity was 262 pA/microm in hypertrophied myocytes from human failing hearts, and it was 143 pA/microm in guinea-pig ventricular myocytes.
  
  
  CONCLUSIONS
  Local stretch of adult single ventricular myocytes can induce arrhythmias that resemble surface-recordings from whole hearts. Stretch modulates multiple current components, I(SAC) being the current with the largest arrhythmogenic potential. Stretch-sensitivity of I(SAC) is higher in hypertrophied than in control myocytes as can be expected from the observation that hypertrophy and failure increase the risk of stretch-induced arrhythmias.
authors.affiliation: Department of Physiology, Martin Luther University, Magdeburgerstrasse 6, D-06097, Halle, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Kamkin
authors.forename: I
authors.initials: I
authors.lastname: Kiseleva
authors.forename: G
authors.initials: G
authors.lastname: Isenberg
mesh_terms: D000200:Action Potentials; D000375:Aging; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007473:Ion Channels / Q000378:metabolism*; D008564:Membrane Potentials; D009206:Myocardium / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013314:Stress, Mechanical; D018754:Ventricular Dysfunction / Q000378:metabolism*
chemical_list: D007473:Ion Channels