Abstract
The Na+/K+ pump is a standard component of cells in higher animals, and there it consumes an estimated 10 to 60% of a cell’s energy production.1 This fraction is so huge that scientists as different as Conway and Ling considered pumps implausible on this basis alone. Such judgments assumed that pumps primarily offset wasteful leakiness. An alternative interpretation emerged from studies cited here: cation gradients are stores of potential energy and are built and maintained to power other cellular functions, notably transport and signalling.
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Notes to Chapter 14
For example, Edelman (1976); Erecinska and Silver (1994); Schramm et al. (1994).
Danielli (1954).
Wilbrandt and Rosenberg (1961).
Cf. Crane and Krane (1956).
Ibid.
Riklis and Quastel (1958).
Csâky and Thale (1960).
McDougal et al. (1960); they suggested a link to Na+ transport, citing Riklis and Quastel. Csâky and Fernald (1961) also localized transport to the luminal surface.
According to his memoir (Crane, 1983), he considered phosphorylation of glucose carriers unlikely since the cell’s mitochondria were so far from the microvilli of the luminal surface.
Crane (1960).
Crane et al. (1961); the model was published as an appendix, and in his 1983 memoir Crane noted that he devised it in Prague shortly before his talk. The experiments were described in detail in Bihler and Crane (1962) and Bihler et al. (1962).
Schultz and Zalusky (1963). Cf. Chapter 6.
Alvarado and Crane (1962).
Schultz and Zalusky (1964b).
Csâky and Zollicoffer (1960), p. 1058; Csâky et al (1961), p. 460; Csâky (1961), p. 1001. Csâky had by then returned to Chapel Hill.
Csâky (1963b), pp. 5, 6.
Ibid., p. 7.
Csâky (1963a), p. 162.
Bihler et al. (1962).
Crane (1964).
Nonmetabolizable sugars were used to prevent their providing cellular energy. In many of the studies cited here, nonmetabolizable sugars were used to avoid artifacts due to concomitant metabolism; one of the most widely used was 3-O-methylglucose, introduced by Csâky (1942).
Garrahan and Glynn had not yet reported reversal of the Na+/K+ pump driven by the ion gradients; an analogous reversal of a Na+-glucose-ATPase could have been occurring in Crane’s experiments.
Csâky and Hara (1965).
Schultz and Zalusky (1964a).
Rose and Schultz (1971).
Hopfer et al. (1973).
Criteria included uptake dependent on intracellular volume (adjusted experimentally by changing osmotic strengths of the media).
If uptake were due to binding, phlorizin should not block both release and uptake.
Murer and Hopfer (1974).
Crane et al. (1976).
Hosang et al. (1981).
Schmidt et al. (1983). Antibodies were prepared using purified brush border membranes as antigens, and fractionated to isolate antibodies blocking sugar transport.
Pearce and Wright (1984, 1985).
Hediger et al. (1987a,b).
For efficiency, various pooled fractions were screened initially.
Christensen and Riggs (1952); Christensen et al. (1952). Ehrlich ascites cells are transplanted into a mouse’s peritoneal cavity where they multiply rapidly as free cells in the ascites fluid.
Christensen et al. (1952), p. 13.
Riggs et al. (1958), p. 1483.
Ibid.
Hempling and Hare (1961).
Kromphardt et al. (1963).
Vidaver (1964).
Csâky (1961).
Schultz and Zalusky (1965).
Schultz and Curran (1970).
Curran et al. (1970).
Philo and Eddy (1978); Heinz et al. (1980).
Koepsell et al. (1984).
Kanai and Hediger (1992). Hediger was the first author on Wright’s expression cloning papers.
Reuter and Seitz (1968); Glitsch et al. (1970).
Baker et al. (1969); Blaustein and Hodgkin (1969), p. 498.
DiPolo (1973).
DiPolo (1978).
Reeves and Sutko (1979); Pitts (1979).
Nicoll et al. (1990).
Crane (1983), pp. 66, 67.
Crane et al. (1965), p. 474. Similar generalizations were made in his influential review (Crane, 1965). Csâky (1961) had proposed analogous transport systems for sugars, amino acids, and pyrimidines-but in terms of ATP-consuming pumps.
Mitchell (1963), p. 148. He also noted that “Crane et al. (1961) have hinted [that] the absorption of sugars… depend [sic] on the asymmetry created by the gradient of Na+ across the cell membrane” (p. 158).
Albers (1967), p. 729.
Mitchell (1963) distinguished between “primary” and “secondary” transport.
Reizer et al. (1994).
Hodgkin and Keynes (1955b), p. 62. Their interpretation dealt with K+ channels, and they did not find it necessary to propose similar characteristics for Na+ channels.
Hodgkin and Huxley (1952d), p. 504.
Armstrong and Bezanilla (1973), p. 459. Their successful measurement relied on computer-averaging of multiple small signals and on blocking the overwhelming Na+ channel current with tetrodotoxin.
Mullins (1960).
Hille (1971, 1972).
Hille (1972), p. 653. Hydrogen bonding proposed between organic solutes and the channel was a rationale for placing oxygens at the selectivity filter.
Eisenman (1962).
Läuger (1973); Hille (1975).
To resolve properties of individual “ion gates” from composite responses of neuromuscular acetylcholine receptors, Katz and Miledi (1972) applied statistical “noise analysis” in conjunction with their kinetic model.
Neher and Sakmann (1976); Hamill et al. (1981). An essential requirement was the high-resistance seal between electrode and membrane: a “gigaOhm seal.”
Goodall et al. (1974); Miller and Racker (1976).
See Narahashi (1974).
Agnew et al. (1980); Hartshorne and Catterall (1981). Molecular weights were estimated by SDS-PAGE. In brain preparations a 38 kDa protein copurified; this was subsequently shown to be a subunit of brain but not electric organ Na+ channels.
Weigele and Barchi (1982); Talvenheimo et al. (1982).
Rosenberg et al. (1984). The next year Catterall and associates reconstituted channels in planar bilayers (Hartshorne et al., 1985).
Noda et al. (1984).
Noda et al. (1986). They expressed mRNA of rat brain Na+ channels whose sequence they also determined.
Guy (1988).
For surveys see Jan and Jan (1989); Hille (1992); and Peracchia (1994).
Biographical information is from Crane (1983).
Crane (1983), p. 51.
Ibid.
Criticisms range from complaints that “data” are accumulated always in the context of some enabling theory to claims that scientists only test hypotheses. Dependence on theory is a critical concern when alternative background theories lead to differently recognized data; in many examples cited here, this seems not to be the case. As for testing hypotheses, any search can be construed this way; for example, when exploring cation effects, this search can be interpreted as testing the hypothesis “cations affect glucose transport” and then measuring all conceivable effects that each cation might have to find which one(s) and how. That, however, is a far cry from testing more discrete hypotheses, such as “an inward gradient of Na+ can alone drive the intracellular accumulation of glucose.”
Crane (1983), p. 48.
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© 1997 American Physiological Society
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Robinson, J.D. (1997). Using the Transmembrane Cation Gradients: Transporters and Channels. In: Moving Questions. People and Ideas Series. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7600-9_14
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