PubMed · 13956713
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
R O IRVINE. 1962. pH at the bedside.. https://pubmed.ncbi.nlm.nih.gov/13956713/
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
Troponin T (TnT) is an essential protein in the Ca2+ regulatory system of striated of muscle. Three fiber type-specific TnT genes have evolved in higher vertebrates to encode cardiac, slow and fast skeletal muscle TnT isoforms. To understand the functional significance of TnT isoforms, we studied the effects of acidosis on the contractility of transgenic mouse cardiac muscle that expresses fast skeletal muscle TnT. Contractility analysis of intact cardiac muscle strips showed that while no differences were detected at physiological pH, the transgenic cardiac muscle had significantly greater decreases in +dF/dtmax at acidic pH than that of the wild-type control. Contractility of skinned cardiac muscles demonstrated that the presence of fast TnT resulted in significantly larger decreases in force and Ca2+ sensitivity at acidic pH than that of the wild-type control. The effect of TnT isoforms on the tolerance of muscle to acidosis may explain the higher tolerance of embryonic versus adult cardiac muscles. The results are consistent with the hypothesis that charge differences in TnT isoforms contribute to the contractility of muscle. The data further support a hypothesis that slow TnT is similar to the cardiac, but not fast, and TnT may contribute to the higher tolerance of slow muscles to stress conditions. Therefore, TnT isoform diversity may contribute to the compatibility of muscle thin filaments to cellular environments in different fiber types, during development and functional adaptation.
Activation of p38 mitogen-activated protein kinase (MAPK) plays a central role in cellular responses to a multitude of stress signals. In the heart, enhanced p38 MAPK signaling has been implicated in cardiac hypoxic and ischemic injury. However, the mechanism underlying hypoxia-induced p38 MAPK activation remains elusive. We investigated p38 MAPK activation during hypoxia in adult rat cardiomyocytes. Here, we reported that hypoxia leads to concurrent intracellular acidosis and activation of p38 MAPK and that the hypoxia-induced p38 MAPK signaling can be fully abolished by neutralizing intracellular pH, whereas intracellular acidosis (intracellular pH<7.0) per se overtly augments activation of p38 MAPK but not ERK1/2 and JNK. Furthermore, inhibition of p38 MAPK protects myocytes against hypoxic cell death, suggesting that acidosis-evoked p38 MAPK signaling plays an important role in hypoxic cell injury and cell death. These results demonstrate, for the first time, that intracellular acidosis constitutes a necessary and sufficient link responsible for hypoxia-activated p38 MAPK signaling and the subsequent hypoxic cardiomyocyte injury and death.
Two-pore-domain potassium channels are a family of ion channels that are widely believed to play an important role in maintaining and regulating neuronal excitability. It has been shown that they can be modulated by an extraordinarily diverse range of endogenous and exogenous factors. One particular member of the family, TREK-1 (also known as KCNK2), is activated by increasing temperature, membrane stretch and internal acidosis, but is also sensitive to the presence of certain polyunsaturated fatty acids (such as arachidonic acid), neuroprotectants (such as riluzole) and volatile and gaseous general anaesthetics (such as halothane and nitrous oxide). It has recently been reported that TREK-1 channels are also affected by oxygen concentrations, and that at the levels of hypoxia that occur in the normal human brain, the channels greatly change their properties and, for example, lose their ability to be modulated by arachidonic acid and internal acidosis. These reports seriously challenge the idea that TREK-1 is a target for general anaesthetics and neuroprotectants. However, in this report we show that TREK-1 is not oxygen sensitive, and its ability to be activated by anaesthetics, arachidonic acid and internal acidosis remains unaltered under conditions of hypoxia. We further show that the protocol used by previous workers to prepare hypoxic solutions of arachidonic acid results in the removal of the compound from solution.