OBJECTIVE: Rabbit ventricular myocardium is characterized by a biphasic response to stretch with an initial, rapid increase in force followed by a delayed, slow increase in force (slow force response, SFR). The initial phase is attributed to increased myofilament Ca(2+) sensitivity, but the mechanisms of the delayed phase are only incompletely understood. We tested whether stretch-dependent stimulation of Na(+)/H(+) exchange (NHE1) and consecutive changes in pH(i) and/or [Na(+)](i) may underlie the SFR. METHODS: Isometric contractions of rabbit ventricular muscles were recorded in bicarbonate-containing Tyrode's (Tyrode) or bicarbonate-free HEPES-buffered solution (HEPES). Muscles were loaded with the Ca(2+) indicator aequorin, the pH indicator BCECF, or the Na(+) indicator SBFI and rapidly stretched from 88% (L(88)) to 98% (L(98)) of optimal length. The resulting immediate and slow increases in twitch force (1st phase and SFR) as well as changes in [Ca(2+)](i), [Na(+)](i), or pH(i) were quantified before and after inhibition of NHE1 by HOE 642 (3 microM) or reverse-mode Na(+)/Ca(2+) exchange (NCX) by KB-R 7943 (5 microM). RESULTS: In both Tyrode (n=21) and HEPES (n=22), developed force increased to approximately 160% during the 1st phase followed by a further increase to approximately 205% during the SFR. The SFR was accompanied by a 21% increase of the aequorin light transient (n=4; normalized to the 1st phase) and a approximately 3 mM increase in [Na(+)](i) (n=4-7). The SFR was also associated with an increase in pH(i). However, this increase was delayed and was significant only after the SFR had reached its maximum. The delayed pH(i) increase was larger in HEPES than in Tyrode. HOE 642 and/or KB-R 7943 reduced the SFR by approximately 30-40%. In addition, HOE 642 diminished the stretch-mediated elevation of [Na(+)](i) by 72% and the delayed alkalinization. CONCLUSIONS: The data are consistent with the hypothesis that SFR results from increases in [Ca(2+)](i) secondary to altered flux via NCX in part resulting from increases in [Na(+)](i) mediated by NHE1.
OBJECTIVE:Rabbit ventricular myocardium is characterized by a biphasic response to stretch with an initial, rapid increase in force followed by a delayed, slow increase in force (slow force response, SFR). The initial phase is attributed to increased myofilament Ca(2+) sensitivity, but the mechanisms of the delayed phase are only incompletely understood. We tested whether stretch-dependent stimulation of Na(+)/H(+) exchange (NHE1) and consecutive changes in pH(i) and/or [Na(+)](i) may underlie the SFR. METHODS: Isometric contractions of rabbit ventricular muscles were recorded in bicarbonate-containing Tyrode's (Tyrode) or bicarbonate-free HEPES-buffered solution (HEPES). Muscles were loaded with the Ca(2+) indicator aequorin, the pH indicator BCECF, or the Na(+) indicator SBFI and rapidly stretched from 88% (L(88)) to 98% (L(98)) of optimal length. The resulting immediate and slow increases in twitch force (1st phase and SFR) as well as changes in [Ca(2+)](i), [Na(+)](i), or pH(i) were quantified before and after inhibition of NHE1 by HOE 642 (3 microM) or reverse-mode Na(+)/Ca(2+) exchange (NCX) by KB-R 7943 (5 microM). RESULTS: In both Tyrode (n=21) and HEPES (n=22), developed force increased to approximately 160% during the 1st phase followed by a further increase to approximately 205% during the SFR. The SFR was accompanied by a 21% increase of the aequorin light transient (n=4; normalized to the 1st phase) and a approximately 3 mM increase in [Na(+)](i) (n=4-7). The SFR was also associated with an increase in pH(i). However, this increase was delayed and was significant only after the SFR had reached its maximum. The delayed pH(i) increase was larger in HEPES than in Tyrode. HOE 642 and/or KB-R 7943 reduced the SFR by approximately 30-40%. In addition, HOE 642 diminished the stretch-mediated elevation of [Na(+)](i) by 72% and the delayed alkalinization. CONCLUSIONS: The data are consistent with the hypothesis that SFR results from increases in [Ca(2+)](i) secondary to altered flux via NCX in part resulting from increases in [Na(+)](i) mediated by NHE1.
Authors: María C Villa-Abrille; Claudia I Caldiz; Irene L Ennis; Mariela B Nolly; María J Casarini; Gladys E Chiappe de Cingolani; Horacio E Cingolani; Néstor G Pérez Journal: J Physiol Date: 2010-03-15 Impact factor: 5.182
Authors: María V Correa; Mariela B Nolly; Claudia I Caldiz; Gladys E Chiappe de Cingolani; Horacio E Cingolani; Irene L Ennis Journal: Pflugers Arch Date: 2013-12-11 Impact factor: 3.657
Authors: Claudia I Caldiz; Carolina D Garciarena; Raúl A Dulce; Leonardo P Novaretto; Alejandra M Yeves; Irene L Ennis; Horacio E Cingolani; Gladys Chiappe de Cingolani; Néstor G Pérez Journal: J Physiol Date: 2007-09-06 Impact factor: 5.182
Authors: Andreas A Werdich; Anna Brzezinski; Darwin Jeyaraj; M Khaled Sabeh; Eckhard Ficker; Xiaoping Wan; Brian M McDermott; Calum A Macrae; David S Rosenbaum Journal: Prog Biophys Mol Biol Date: 2012-07-23 Impact factor: 3.667
Authors: Jens Kockskämper; Mounir Khafaga; Michael Grimm; Andreas Elgner; Stefanie Walther; Anke Kockskämper; Dirk von Lewinski; Heiner Post; Marius Grossmann; Hilmar Dörge; Philip A Gottlieb; Frederick Sachs; Thomas Eschenhagen; Friedrich A Schöndube; Burkert Pieske Journal: Cardiovasc Res Date: 2008-05-24 Impact factor: 10.787
Authors: Jens Kockskämper; Dirk von Lewinski; Mounir Khafaga; Andreas Elgner; Michael Grimm; Thomas Eschenhagen; Philip A Gottlieb; Frederick Sachs; Burkert Pieske Journal: Prog Biophys Mol Biol Date: 2008-03-14 Impact factor: 3.667