title: Stretch-dependent slow force response in isolated rabbit myocardium is Na+ dependent.
abstract: OBJECTIVE
  Stretch induces functional and trophic effects in mammalian myocardium via various signal transduction pathways. We tested stretch signal transduction on immediate and slow force response (SFR) in rabbit myocardium.
  
  
  METHODS
  Experiments were performed in isolated right ventricular muscles from adult rabbit hearts (37 degrees C, 1 Hz stimulation rate, bicarbonate-buffer). Muscles were rapidly stretched from 88% of optimal length (L88) to near optimal length (L98) for functional analysis. The resulting immediate and slow increases in twitch force (first phase and SFR, respectively) were assessed at reduced [Na+]o or without and with blockade of stretch activated ion channels (SACs), angiotensin-II (AT1) receptors, endothelin-A (ET(A)) receptors, Na+/H+-exchange (NHE1), reverse mode Na+/Ca2+-exchange (NCX), or Na+/K+-ATPase. The effects of stretch on sarcoplasmic reticulum Ca2+-load were characterized using rapid cooling contractures (RCCs). Intracellular pH was measured in BCECF-AM loaded muscles, and action potential duration (APD) was assessed using floating electrodes.
  
  
  RESULTS
  On average, force increased to 216+/-8% of the pre-stretch value during the immediate phase, followed by a further increase to 273+/-10% during the SFR (n=81). RCCs significantly increased during SFR, whereas pH and APD did not change. Neither inhibition of SACs, AT1, or ET(A) receptors affected the stretch-dependent immediate phase nor SFR. In contrast, SFR was reduced by NHE inhibition and almost completely abolished by reduced [Na+]o or inhibition of reverse-mode NCX, whereas increased SFR was seen after raising [Na+]i by Na+/K+-ATPase inhibition.
  
  
  CONCLUSIONS
  The data demonstrate the existence of a delayed, Na+- and Ca2+-dependent but pH and APD independent SFR to stretch in rabbit myocardium. This inotropic response appears to be independent of autocrine/paracrine AT1 or ET(A) receptor activation, but mediated through stretch-induced activation of NHE and reverse mode NCX.
authors.affiliation: Department of Cardiology and Pneumology, Georg-August-University, Robert-Koch-Str. 40, 37075, Göttingen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: von Lewinski
authors.forename: Burkhard
authors.initials: B
authors.lastname: Stumme
authors.forename: Lars S
authors.initials: LS
authors.lastname: Maier
authors.forename: Claus
authors.initials: C
authors.lastname: Luers
authors.forename: Donald M
authors.initials: DM
authors.lastname: Bers
authors.forename: Burkert
authors.initials: B
authors.lastname: Pieske
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D046508:Culture Techniques; D006863:Hydrogen-Ion Concentration; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D009200:Myocardial Contraction / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D012964:Sodium / Q000502:physiology*; D019831:Sodium-Calcium Exchanger / Q000502:physiology; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology; D013314:Stress, Mechanical
chemical_list: D019831:Sodium-Calcium Exchanger; D017923:Sodium-Hydrogen Exchangers; D012964:Sodium; D002118:Calcium