title: Contribution of NHE-1 to cell length shortening of normal and failing rabbit cardiac myocytes.
abstract: At the same intracellular pH (pHi) Na+/H+ exchange (NHE-1) fluxes of ventricular myocytes of hypertrophied failing hearts (HFH) are increased. We assessed how NHE-1 affected cell length shortening. pHi was measured fluorimetrically in resting and twitching (1-3 Hz) normal and HFH rabbit myocytes. In HEPES-buffered solutions, increased NHE-1 fluxes (P=0.001, n=14) made HFH resting pHi 0.2+/-0.03 units more alkaline than control (n=27). In CO2/HCO3--buffered solutions, HFH resting pHi was not different (7.05+/-0.02, n=30). Twitching myocytes of both groups shortened 15-16% less per 0.1 pH unit acidification. In HEPES-buffered solutions, cariporide depressed cell length shortening of normal myocytes (1-3 Hz) by 16+/-5.4% (n=9, P=0.005). In HFH myocytes cariporide restored the positive force-frequency relationship (n=7, P=0.009), by depressing twitch amplitudes at 1 Hz (16+/-11%, P=0.047) but not at 2 and 3 Hz. The depressions were all caused by pHi acidification. In CO2/HCO3- buffered solutions the cariporide-induced acidification was too small to explain the cell length shortening depression of normal (19+/-5.0%, n=11, P=0.006) and HFH myocytes (14+/-4.7%, n=11, P=0.001). When compared to HEPES-buffered solutions, HFH myocytes in CO2/HCO3--buffered solutions shortened 12+/-6.8% better than expected given the 0.16+/-0.02 units more acidic pHi's at which they twitched. We conclude that in CO2/HCO3--buffered solutions NHE-1 improved cell length shortening of unstretched normal and HFH myocytes via a pHi-independent mechanism. Although NHE-1 was increased in HFH myocytes, the magnitude of the pHi-independent effect of NHE-1 inhibition on cell length shortening was similar in both groups.
authors.affiliation: Department of Physiology, University of Amsterdam, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands. m.m.vanborren@amc.uva.nl
authors.forename: Marcel M G J
authors.initials: MM
authors.lastname: van Borren
authors.forename: Jan G
authors.initials: JG
authors.lastname: Zegers
authors.forename: Antonius
authors.initials: A
authors.lastname: Baartscheer
authors.forename: Jan H
authors.initials: JH
authors.lastname: Ravesloot
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000494:pharmacology; D002245:Carbon Dioxide / Q000494:pharmacology; D006332:Cardiomegaly / Q000503:physiopathology*; D049108:Cell Enlargement; D048429:Cell Size; D006531:HEPES / Q000494:pharmacology; D006352:Heart Ventricles / Q000166:cytology / Q000503:physiopathology*; D006863:Hydrogen-Ion Concentration; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000502:physiology*; D011817:Rabbits; D017923:Sodium-Hydrogen Exchangers / Q000502:physiology*
chemical_list: D001639:Bicarbonates; D017923:Sodium-Hydrogen Exchangers; C069139:growth factor-activatable Na-H exchanger NHE-1; D002245:Carbon Dioxide; D006531:HEPES