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J Physiol Volume 535, Number 2, 407-417, September 1, 2001
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Journal of Physiology (2001), 535.2, pp. 407-417
© Copyright 2001 The Physiological Society

Heterologous expression of the Na+,K+-ATPase gamma subunit in Xenopus oocytes induces an endogenous, voltage-gated large diameter pore


Qun Sha, Kristan L. Lansbery, Darcy Distefano, Robert W. Mercer and Colin G. Nichols


Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA

  1. The gamma subunit is a specific component of the plasmalemmal Na+,K+-ATPase. Like structurally related single-spanning membrane proteins such as cardiac phospholemman, Mat-8 and renal CHIF, large ion conductances are activated when gamma subunits are expressed in Xenopus oocytes.
  2. Here we report critical properties of the gamma-activated conductance. The gamma-activated conductance showed non-selective cationic and anionic permeation, and extremely slow kinetics, with an activation time constant > 1 s following steps to -100 mV.
  3. The gamma-activated conductance was inhibited by extracellular divalent ions including Ba2+ (Ki = 0.7 mM) and Ca2+ (Ki = 0.4 mM).
  4. 2-Deoxyglucose (MW ~180), inulin (MW ~5000) and spermidine (MW ~148) efflux could occur through the gamma-activated conductance pathway, indicating a large pore diameter. In contrast, dextran-70 (MW ~70 000) did not pass through the gamma-activated channel, indicating an upper limit to the pore size of ~50 Å (5 nm).
  5. Similar conductances that are permeable to large molecules were activated by extreme hyperpolarization (> -150 mV) of uninjected oocytes.
  6. We conclude that the Na+,K+-ATPase gamma subunits activate Ca2+- and voltage-gated, non-selective, large diameter pores that are intrinsically present within the oocyte membrane.



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