Na-H exchange in myocardium: effects of hypoxia and acidification on Na and Ca

Abstract

Historically, increase in cell Na content during ischemic and hypoxic episodes were thought to result from impaired ATP production causing decreased Na(+)-K(+)-ATPase activity. Here we report the results of testing the alternate hypothesis that hypoxia-induced Na uptake is 1) the result of increased entry, as opposed to decreased extrusion 2) via Na-H exchange operating in a pH regulatory capacity and that cell Ca accumulation occurs via Na-Ca exchange secondary to collapse of the Na gradient. We used 23Na-, 19F-, and 31P-nuclear magnetic resonance (NMR) to measure intracellular Na content (Nai), Ca concentration [( Ca]i), pH (pHi), and high-energy phosphates in Langendorff-perfused rabbit hearts. When the Na(+)-K(+)-ATPase was inhibited by ouabain and/or K-free perfusion, hearts subjected to hypoxia gained Na at a rate greater than 10 times that of normoxic controls [during the first 12.5 min Nai increased from 7.9 +/- 5.8 to 34.9 +/- 11.0 (SD) meq/kg dry wt compared with 11.1 +/- 16.3 to 13.6 +/- 9.0 meq/kg dry wt, respectively]. When normoxic hearts were acidified using a 20 mM NH4Cl prepulse technique, pHi rapidly fell from 7.27 +/- 0.24 to 6.63 +/- 0.12 but returned to 7.07 +/- 0.10 within 20 min, while Na uptake was similar in rate and magnitude to that observed during hypoxia (24.5 +/- 13.4 to 132.1 +/- 17.7 meq/kg dry wt). During hypoxia and after NH4Cl washout, increases in [Ca]i were similar in time course to those observed for Na.(ABSTRACT TRUNCATED AT 250 WORDS)

Polyol pathway and modulation of ischemia-reperfusion injury in Type 2 diabetic BBZ rat hearts

“…Several studies have shown that the attenuation of the rise in EDP by interventions is linked to the maintenance of intracellular sodium and calcium homeostasis [44][45][46][47][48][49]. In our earlier studies, we have shown that inhibition of aldose reductase attenuated the rise in intracellular sodium and calcium during ischemia and reperfusion in Type 1 BB/WOR diabetic hearts [48].…”

Enhanced gene expression of Na+/Ca2+exchanger attenuates ischemic and hypoxic contractile dysfunction

“…When the internal pH of cardiac cells is lowered, as occurs during ischemia and hypoxia, Na ϩ /H ϩ exchange becomes the major regulatory system by which cells recover from acidosis (25). Accumulation of H ϩ has been shown to mediate a rise in Na ϩ by activation of the Na ϩ /H ϩ exchanger (3,25). Inhibition of the Na ϩ /K ϩ -ATPase activity during hypoxia markedly increases Na ϩ accumulation (3).…”

Acute effects of 17β-estradiol on myocardial pH, Na+, and Ca2+ and ischemia-reperfusion injury

“…The methods used were modified from those previously reported (3,6,31). Briefly, 12-to 13-wk-old ovariectomized Sprague-Dawley rats (OVX) were purchased from Charles River 1 wk after ovariectomy.…”

“…This method measures Na i ϩ as an amount, and to minimize assumptions, we report it as such. [Ca 2ϩ ]i (in nmol/l cytosolic water) was calculated as the product of the Ca 2ϩ -FBAPTA dissociation constant (Kd) and the ratio of the areas of the Ca 2ϩ -bound and Ca 2ϩ -free peaks in the FBAPTA spectrum (6). The Kd for Ca 2ϩ -FBAPTA was 294 nM.…”

“…pHi was determined from the chemical shift of the inorganic phosphate (Pi) resonance (with reference to control phosphocreatine) calibrated at 37°C (2). High-energy phosphates are reported as percentage of control peak intensity (6).…”