Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2192357 | Journal of Molecular and Cellular Cardiology | 2006 | 10 Pages |
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/HCO3â-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/HCO3â 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/HCO3â-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/HCO3â-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.
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Authors
Marcel M.G.J. van Borren, Jan G. Zegers, Antonius Baartscheer, Jan H. Ravesloot,