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I am extremely honored and pleased to have the opportunity to write a few introductory words for this timely volume on Na + /It exchange. This is a field of investigation that I entered into by challenge and necessity, embraced with passion and fmally left in my quest for new discoveries in growth control. Ten years, one third of my scientific life, has been devoted to uncovering the mysteries of intracellular pH (PH;) regulation with respect to growth factor action. I got started on this new topic in 1980, when I heard a rather provocative hypothesis presented by Enrique Rozengurt at an ICN-UCLA Keystone meeting on "Cell Surface and Malignancy". He showed that all mitogens induced amiloride-sensitive Na + entry into resting cells and proposed that, if a compound stimulates Na + influx, it could be a mitogen. In support of his proposal Enrique reported that the amphipathic polypeptide, mellitin, which induced Na+ influx, was indeed mitogenic for 3T3 cells. This was only correlation at this stage. However, I was fascinated by this talk. I immediately approached Enrique to inform him of my skepticism about this beautiful story, and to indicate that I would only be convinced when I succeeded in isolating mutant fibroblasts lacking the amiloride-sensitive Na+ transporter. ''Good luck!" was his response.
Contents
1: Regulation of Intracellular pH in Mammalian Cells. 1. Introduction. 2. Intracellular Compartmentalization Of pH. 3. Cytoplasmic pH. 4. Intracellular Buffers. 5. Measurement Of pHi During Acid-Base Loading. 6. Transport Systems That Regulate pHi.
2: Molecular and Functional Diversity of Mammalian Na+/H+ Exchangers. 1. Introduction. 2. Genetic Heterogeneity. 3. Conclusion.
3: Two Functional Regulatory Factors of Na+/H+ Exchangers: The Proton and aHP. 1. Introduction. 2. The Proton. 3. CHP. 4. Conclusion.
4: Regulation of Expression of the Na+/H+ Exchanger in the Myocardium and Other Tissues. 1. Introduction. 2. Na+/H+ Exchanger Expression Varies In Response To The Environment. 3. Transcriptional Regulation Of The Na+/H+ Exchanger Gene. 4. Conclusion.
5: Na-H Exchange Function in Colonic Epithelial Cells. 1. Introduction. 2. Apical Membrane NHEs. 3. Basolateral Membrane NHEs.
6: NhaA Na+/H+Antiporter. Structure, Mechanism and Function in Homestasis of Na+ and pH. 1. Introduction. 2. The Response to Na+ Occurs At The Transcription Level. 3. The Ecological Importance Of The Antiporters In The Enteric Bacteria Escherichia coli And Vibrio cholerae. 4. The NhaA Protein. 5. Relationship Between Function And Structure Of NhaA. 6. Dynamics Of NhaA. 7. Dynamics In 3D Of The pH Induced Conformational Changes Of NhaA. 8. Conclusion.
7: The Use of Transgenic Animal Models to Study Na+/H+ Exchange. 1. Introduction. 2. Transgenic Studies On The NHE1 Isoform Of The Na+/H+ Exchanger. 3. Transgenic Studies On The NHE2 And NHE3 Isoform Of Na+/H+ Exchanger. 4. Pitfalls In Transgenic Studies. 5. Conclusion.
8: pH-Regulatory Mechanisms in the Mammalian Oocyte and Early Embryo. 1. Introduction. 2. Oocyte And Embryo Development. 3. Expression Of Na+/H+ Exchanger (NHE) And Anion Exchanger (AE) Isoforms In Mammalian PI Embryos. 4. Activity Of pHi-Regulatory Mechanism In PI Embryos. 5. pHiRegulatory Mechanisms During Meiosis And Fertilization. 6. Conclusion.
9: Na+/H+ Exchanger Activation by Myocardial Stretch. 1. Introduction. 2. Mechanism Of Stretch-Induced Increase Of The NHE Activity. 3. Mechanical Counterpart Of Stretch-Induced Increase Of The NHE Activity.
10: The Paradoxical Role of Na+/H+ Exchanger in the Diabetic Heart. 1. Introduction. 2. Depressed Na+/H+ Exchanger (NHE) Activity In Insulin-Deficient (TYPE I) Diabetes And Associated Increased Resistance Of Diabetic Hearts To Ischemia And Reperfusion Injury. 3. NHE In Non-Insulin-Dependent (TYPE 2) Diabetes. 4. Conclusion.
11: Role of Na-H Exchanger in Vascular Remodelling in
