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Role of Na[sup +]/H[sup +] exchanger during O[sub 2] deprivation in mouse CA1 neurons. Am J Physiol Cell Physiol 281: C1205-C1210, 2001.—To determine the role of membrane transporters in intracellular pH (pH[sub i]) regulation under conditions of low microenvironmental O[sub 2], we monitored phi in isolated single CA1 neurons using the fluorescent indicator carboxyseminaphthorhodafluor-1 and confocal microscopy. After total O[sub 2] deprivation or anoxia (Po[sub 2] ≅ 0 Torr), a large increase in phi was seen in CA1 neurons in HEPES buffer, but a drop in phi, albeit small, was observed in the presence of HCO[sup -, sub 3]. Ionic substitution and pharmacological experiments showed that the large anoxia-induced pH[sub i] increase in HEPES buffer was totally Na[sup +] dependent and was blocked by HOE-694, strongly suggesting the actiration of the Na[sup +]/H[sup +] exchanger (NHE). Also, this pH[sub i] increase in HEPES buffer was significantly smaller in Na[sup +]/H[sup +] exchanger isoform 1 (NHE1) null mutant CA1 neurons than in wild-type neurons, demonstrating that NHE1 is responsible for part of the pH[sup i] increase following anoxia. Both chelerythrine and H-89 partly blocked, and H-7 totally eliminated, this anoxia-induced pH[sup i] increase in the absence of HCO[sup -, sub 3]. We conclude that 1) O[sub 2] deprivation activates Na[sup +]/H[sup +] exchange by enhancing protein kinase activity and 2) membrane proteins, such as NHE, actively participate in regulating pH[sup i] during low-O[sup 2] states in neurons. [ABSTRACT FROM AUTHOR]

Demonstrates the existence of an important functional interaction between the sodium/hydrogen exchanger isoform 1 (NHE1) protein and the voltage-sensitive sodium channel in mice. Manifestation of neurological diseases; Hippocampal neuron functioning; Mechanisms for increased excitability in mutant NHE1 neurons; Interaction disturbance of specific proteins in neuron membrane.