Interactions of amiloride and other blocking cations with the apical Na channel in the toad urinary bladder (original) (raw)

Summary

A simple model of the action of amiloride to block apical Na channels in the toad urinary bladder was tested. According to the model, the positively charged form of the drug binds to a site in the lumen of the channel within the electric field of the membrane. In agreement with the predictions of the model: (1) The voltage dependence of amiloride block was consistent with the assumption of a single amiloride binding site, at which about 15% of the transmembrane voltage is sensed, over a voltage range of ±160 mV. (2) The time course of the development of voltage dependence was consistent with that predicted from the rate constants for amiloride binding previously determined. (3) The ability of organic cations to mimic the action of amiloride showed a size dependence implying a restriction of access to the binding site, with an effective diameter of about 5 angstroms. In a fourth test, divalent cations (Ca, Mg, Ba and Sr) were found to block Na channels with a complex voltage dependence, suggesting that these ions interact with two or more sites. at least one of which may be within the lumen of the pore.

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References

• Benos, D.J. 1982. Amiloride: A molecular probe of sodium transport in tissues and cells.Am. J. Physiol. 242:C131-C145
  Google Scholar
• Cuthbert, A.W. 1976. Importance of guanidinium groups for blocking sodium channels in epithelia.Mol. Pharmacol. 12:945–957
  Google Scholar
• Hille, B. 1975. Ionic selectivity of Na and K channels of nerve membranes.In: Membranes: A Series of Advances. Volume 3: Dynamic properties of lipid bilayers and biological membranes. G. Eisenmann, editor. pp. 255–323. Marcel Dekker, New York
  Google Scholar
• Latorre, R., Miller, C. 1983. Conduction and selectivity in potassium channels.J. Membrane Biol. 71:11–30
  Google Scholar
• Li, J.H.-Y., Palmer, L.G., Edelman, I.S., Lindemann, B. 1982. The role of sodium-channel density in the natriferic response of the toad urinary bladder to an antidiuretic hormone.J. Membrane Biol. 64:77–89
  Google Scholar
• Miller, C. 1982. Bis-quaternary ammonium blockers as structural probes of the sarcoplasmic reticulum K+ channel.J. Gen. Physiol. 79:869–891
  Google Scholar
• Palmer, L.G. 1982_a_. Ion selectivity of the apical membrane Na channel in the toad urinary bladder.J. Membrane Biol. 67:91–98
  Google Scholar
• Palmer, L.G. 1982_b_. Na+ transport and flux ratio through apical Na+ channels in toad urinary bladder.Nature (London) 297:688–690
  Google Scholar
• Palmer, L.G. 1984. Voltage-dependent block by amiloride and other monovalent cations of apical Na channels in the toad urinary bladder.J. Membrane Biol. 80:153–165
  Google Scholar
• Palmer, L.G. 1985. Modulation of apical Na permeability of the toad urinary bladder by intracellular Na, Ca and H.J. Membrane Biol. 83:57–69
  Google Scholar
• Palmer, L.G., Edelman, I.S., Lindemann, B. 1980. Current-voltage analysis of apical sodium transport in toad urinary bladder: Effects of inhibitors of transport and metabolism.J. Membrane Biol. 57:59–71
  Google Scholar
• Palmer, L.G., Lorenzen, M. 1983. Antidiuretic hormone-dependent membrane capacitance and water permeability in the toad urinary bladder.Am. J. Physiol. 244:F195-F204
  Google Scholar
• Warncke, J., Lindemann, B. 1981. Effect of ADH on the capacitance of apical epithelial membranes.Adv. Physiol. Sci. 3:129–133
  Google Scholar
• Warncke, J., Lindemann, B. 1985. Voltage-dependence of Na channel blockage by amiloride: Relaxation effects in admittance spectra.J. Membrane Biol. (in press)
• Woodhull, A.M. 1973. Ionic blockage of sodium channels.J. Gen. Physiol. 61:687–708
  Google Scholar

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1. Department of Physiology, Cornell University Medical College, 10021, New York, New York
   Lawrence G. Palmer

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1. Lawrence G. Palmer
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Palmer, L.G. Interactions of amiloride and other blocking cations with the apical Na channel in the toad urinary bladder.J. Membrain Biol. 87, 191–199 (1985). https://doi.org/10.1007/BF01871218

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• Received: 16 October 1984
• Revised: 24 May 1985
• Issue Date: October 1985
• DOI: https://doi.org/10.1007/BF01871218

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