Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Luers, C; Fialka, F; Elgner, A; Zhu, D; Kockskämper, J; von Lewinski, D; Pieske, B.
Stretch-dependent modulation of Na+i, Ca2+i, and pHi in rabbit myocardium--a mechanism for the slow force response.
Cardiovasc Res. 2005; 68(3):454-463
Doi: 10.1016/j.cardiores.2005.07.001
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- Führende Autor*innen der Med Uni Graz
- Pieske Burkert Mathias
- Co-Autor*innen der Med Uni Graz
- Kockskämper Jens
- von Lewinski Dirk
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- Abstract:
- 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 Ca2+ sensitivity, but the mechanisms of the delayed phase are only incompletely understood. We tested whether stretch-dependent stimulation of Na+/H+ exchange (NHEI) 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 Ca2+ 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 [Ca2+](i), [Na+](i), or pH(i) were quantified before and after inhibition of NHE I by HOE 642 (3 mu M) or reverse-mode Na+/Ca2+ exchange (NCX) by KB-R 7943 (5 mu M). Results: In both Tyrode (n=21) and HEPES (n=22), developed force increased to similar to 160% during the 1st phase followed by a further increase to similar to 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 similar to 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 pHi increase was larger in HEPES than in Tyrode. HOE 642 and/or KB-R 7943 reduced the SFR by similar to 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 [Ca2+](i) secondary to altered flux via NCX in part resulting from increases in [Na+]i mediated by NHE1 (c) 2005 European Society of Cardiology. Published by Elsevier B.V All rights reserved.
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- E-c coupling
- stretch
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