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Deprecated: Implicit conversion from float 211.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Am+J+Physiol+Regul+Integr+Comp+Physiol 2014 ; 307 (12): R1413-27 Nephropedia Template TP
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Effects of metabolic acidosis on intracellular pH responses in multiple cell types #MMPMID25209413
Salameh AI; Ruffin VA; Boron WF
Am J Physiol Regul Integr Comp Physiol 2014[Dec]; 307 (12): R1413-27 PMID25209413show ga
Metabolic acidosis (MAc), a decrease in extracellular pH (pHo) caused by a decrease in [HCO3?]o at a fixed [CO2]o, is a common clinical condition and causes intracellular pH (pHi) to fall. Although previous work has suggested that MAc-induced decreases in pHi (?pHi) differ among cell types, what is not clear is the extent to which these differences are the result of the wide variety of methodologies employed by various investigators. In the present study, we evaluated the effects of two sequential MAc challenges (MAc1 and MAc2) on pHi in 10 cell types/lines: primary-cultured hippocampal (HCN) neurons and astrocytes (HCA), primary-cultured medullary raphé (MRN) neurons, and astrocytes (MRA), CT26 colon cancer, the C2C12 skeletal muscles, primary-cultured bone marrow-derived macrophages (BMDM) and dendritic cells (BMDC), Ink4a/ARF-null melanocytes, and XB-2 keratinocytes. We monitor pHi using ratiometric fluorescence imaging of 2?,7?-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein while imposing MAc: lowering (pHo) from 7.4 to 7.2 by decreasing [HCO3?]o from 22 to 14 mM at 5% CO2 for 7 min. After MAc1, we return cells to the control solution for 10 min and impose MAc2. Using our definition of MAc resistance [(?pHi/?pHo) ? 40%], during MAc1, ?70% of CT26 and ?50% of C2C12 are MAc-resistant, whereas the other cell types are predominantly MAc-sensitive. During MAc2, some cells adapt [(?pHi/?pHo)2 < (?pHi/?pHo)1], particularly HCA, C2C12, and BMDC. Most maintain consistent responses [(?pHi/?pHo)2 ? (?pHi/?pHo)1], and a few decompensate [(?pHi/?pHo)2>(?pHi/?pHo)1], particularly HCN, C2C12, and XB-2. Thus, responses to twin MAc challenges depend both on the individual cell and cell type.