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      저자 : Vaughan-Jones, R.D. (검색결과 1 건)
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        Experimental Generation and Computational Modeling of Intracellular pH Gradients in Cardiac Myocytes

        Swietach, P.,Leem, C.H.,Spitzer, K.W.,Vaughan-Jones, R.D. Biophysical Society ; Published for the Biophysica 2005 Biophysical journal Vol.88 No.4

        It is often assumed that pH<SUB>i</SUB> is spatially uniform within cells. A double-barreled microperfusion system was used to apply solutions of weak acid (acetic acid, CO<SUB>2</SUB>) or base (ammonia) to localized regions of an isolated ventricular myocyte (guinea pig). A stable, longitudinal pH<SUB>i</SUB> gradient (up to 1pH<SUB>i</SUB> unit) was observed (using confocal imaging of SNARF-1 fluorescence). Changing the fractional exposure of the cell to weak acid/base altered the gradient, as did changing the concentration and type of weak acid/base applied. A diffusion-reaction computational model accurately simulated this behavior of pH<SUB>i</SUB>. The model assumes that H<SUB>i</SUB><SUP>+</SUP> movement occurs via diffusive shuttling on mobile buffers, with little free H<SUP>+</SUP> diffusion. The average diffusion constant for mobile buffer was estimated as 33x10<SUP>-7</SUP>cm<SUP>2</SUP>/s, consistent with an apparent H<SUB>i</SUB><SUP>+</SUP> diffusion coefficient, D<SUB>H</SUB><SUP>app</SUP>, of 14.4x10<SUP>-7</SUP>cm<SUP>2</SUP>/s (at pH<SUB>i</SUB> 7.07), a value two orders of magnitude lower than for H<SUP>+</SUP> ions in water but similar to that estimated recently from local acid injection via a cell-attached glass micropipette. We conclude that, because H<SUB>i</SUB><SUP>+</SUP> mobility is so low, an extracellular concentration gradient of permeant weak acid readily induces pH<SUB>i</SUB> nonuniformity. Similar concentration gradients for weak acid (e.g., CO<SUB>2</SUB>) occur across border zones during regional myocardial ischemia, raising the possibility of steep pH<SUB>i</SUB> gradients within the heart under some pathophysiological conditions.

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