Intracellular
            <i>p</i>
            H of Mitogen-Stimulated Lymphocytes

Gerson, Donald F.; Kiefer, H.; Eufe, Wolfgang

doi:10.1126/science.6281887

Cited by 115 publications

(55 citation statements)

References 11 publications

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“…including lymphocytes (Gerson, Kiefer & Eufe, 1982). Changes in intracellular pH have been observed in lymphocytes and thvmocvtes in both the short-term and long-term response to mitogens (Gerson et al 1982: Deutsch. Taylor & Price, 1984 Hesketh, Mloore.…”

Section: Many Investigators Have Postulated That Intracellular [H+] Rmentioning

confidence: 99%

Modulation of K+ currents in human lymphocytes by pH.

Deutsch

Lee

1989

The Journal of Physiology

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SUMMARY1. Using whole-cell patch-clamp techniques, we found that the voltage-dependent K+ conductance in human peripheral blood T lymphocytes is enhanced threefold at alkaline intracellular pH (pHi) compared to acid pHi. This pH dependence can be described by a model having two strongly co-operative proton binding sites with pKa 7 15. A similar pHi sensitivity exists for K+ conductance in mitogen-activated cells.2. The reversal potential, threshold voltage for activation of the K+ conductance, and voltage dependence of steady-state inactivation are not affected by pHi.Activation and inactivation kinetics are also unchanged.3. Single-channel measurements made in whole-cell patch-clamp mode indicate that the effect of intracellular pH on the amplitudes of single-channel events parallels, but does not wholly account for, the effect of pHi on the macroscopic currents.4. Lowering extracellular pH (pHO) shifts the threshold for activation of the K+ current to a more depolarized voltage, consistent with a surface charge screening effect. Apparent changes in peak current and activation kinetics at acid pHo can be accounted for by this voltage shift. An additional slowing of inactivation kinetics at low pHo does occur.5. The relevance of the pH sensitivity of the voltage-gated K+ conductance to lymphocyte mitogenesis and volume regulation is discussed.

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Section: Many Investigators Have Postulated That Intracellular [H+] Rmentioning

confidence: 99%

Modulation of K+ currents in human lymphocytes by pH.

Deutsch

Lee

1989

The Journal of Physiology

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“…Direct methods of measuring pHi or [Cali have been limited mainly to large cells in which it is possible to insert microelectrodes or inject indicators (e.g., aequorin) into individual cells. Methods for measurement in small cells have mainly relied on indirect assays, for example the partition of 5,5dimethyl oxazolidine-2,4-dione (DMO) to measure pHi [1,2]. This has impeded analysis of the coupling of ionic signals to biological responses in many important cellular systems.…”

Section: Introductionmentioning

confidence: 99%

Intracellular pH and free calcium changes in single cells using quene 1 and quin 2 probes and fluorescence microscopy

et al. 1983

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Photometric fluorescence microscopy has been used to measure intracellular pH (pHi) and free calcium concentrations ([Ca]i) in individual mouse thymocytes and 2H3 rat basophil leukaemic cells containing indicators for pH (quene 1) or calcium (quin 2). The pHi and [Ca]i measurements in individual 2H3 cells and mouse thymocytes and their responses to various stimuli were consistent with the corresponding data obtained from suspensions of these cells measured in a spectrofluorimeter. Photometric fluorescence microscopy of these indicators in individual cells provides a sensitive and fast method of following pHi and [Ca]i responses in individual cells.

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“…pHi is certainly capable of affecting the activity of many cellular processes (25) and has been implicated in the metabolic control of many types of cellular activity, including fertilization (8), germination (29), cell division (1 1, 13), and mitotic activation (12).…”

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Changes in Intracellular pH Are Not Correlated with the Circadian Rhythm of Neurospora

Johnson

1983

Plant Physiol.

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Intracellular pH (pHi) was measured during the circadian cycle of Neurospora. Internal pH of Neurospora cultures in liquid medium was assayed by the 5,5-dimethyl-2,4-oxazolidinedione method and gave values for pHi which were similar to those previously obtained by other workers using pH-microelectrodes with agar-grown cultures. Cytoplasmic pH changed in liquid medium cultures, but these changes were not related to the circadian clock. Furthermore, treatments which raise or lower pHi do not phase-shift the circadian rhythm. These results indicate that pHi plays no specific role in regulating the circadian clock of Neurospora.Circadian rhythms modulate an enormous variety of biological phenomena and have interested biologists ever since the first observations by De Mairan (5). Despite energetic efforts within the past 25 years to reveal the mechanism of the biological 'clock,' however, little has been discovered about its cellular basis (14). For example, circadian oscillations in the activity of many enzymes have been reported, but each of these appears to be a clockcontrolled parameter (a 'hand of the clock') rather than a component of the 'clockworks.'A reasonable approach to track down the mechanism of the clock would be to identify intracellular parameters which (a) affect the activity of other cellular processes and (b) fluctuate rhythmically in phase with the clock. Such parameters could function as synchronizers or 'coupling factors' between the clock and the processes it controls. It is conceivable that the clockworks itself could then be discerned by tracing backwards the pathways by which these hypothetical parameters are regulated.I decided to test whether pHi' might qualify as such a coupling factor to the clock. pHi is certainly capable of affecting the activity of many cellular processes (25) and has been implicated in the metabolic control of many types of cellular activity, including fertilization (8), germination (29), cell division (1 1, 13), and mitotic activation (12).In addition, a number of studies suggest that pHi might specifically be involved in the clockworks. First, two multicellular organisms show daily rhythms of their pHo (coelomic): the cockroach Leucophaea maderae (20) and the sea-pen Cavernularia obesa (21). Because the pHi and pHo of multicellular organisms are often regulated so that the pH difference between them remains constant (23), the observation that pHo is rhythmic suggests that pHi might be cyclic as well. In fact, subsequent work on the sea-pen has shown that the injection of acidic sea water into 'Abbreviations: pHi, intracellular pH; pH,, extracellular pH; pan, pantothenic acid; DMO, 5,5-dimethyl-2,4-oxazolidinedione; LL, constant light (500 lux); DD, constant darkness; T, period of the circadian rhythm.the coelom causes a phase-shift of the rhythm (15), indicating that pH can exert a feedback effect on the clock.Second, temperature changes are known to phase-shift rhythms (for Neurospora, see Ref. 9) and to perturb pHi (23). Thus, temperature changes might ...

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Intracellular p H of Mitogen-Stimulated Lymphocytes

Cited by 115 publications

References 11 publications

Modulation of K+ currents in human lymphocytes by pH.

Modulation of K+ currents in human lymphocytes by pH.

Intracellular pH and free calcium changes in single cells using quene 1 and quin 2 probes and fluorescence microscopy

Changes in Intracellular pH Are Not Correlated with the Circadian Rhythm of Neurospora

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