Interaction of the Na+-K+ pump and Na+-Ca2+ exchange via [Na+]i in a restricted space of guinea-pig ventricular cells

• Published in: The Journal of physiology 1998-06, Vol.509 (2), p.457-470
• Main Authors: Fujioka, Yasutada, Matsuoka, Satoshi, Ban, Toshihiko, Noma, Akinori
• Format: Article
• Language: English
• Subjects: Animals; Calcium - pharmacology; Cell Membrane - physiology; Cells, Cultured; Egtazic Acid - pharmacology; Guinea Pigs; Heart - physiology; Heart Ventricles; Kinetics; Membrane Potentials - drug effects; Models, Biological; Myocardium - metabolism; Original; Patch-Clamp Techniques; Sarcolemma - metabolism; Sodium - metabolism; Sodium-Calcium Exchanger - metabolism; Sodium-Potassium-Exchanging ATPase - metabolism
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1111/j.1469-7793.1998.457bn.x

The whole-cell Na + -K + pump current ( I Na-K ) and Na + -Ca 2+ exchange current ( I Na-Ca ) were recorded in guinea-pig ventricular myocytes to study the interaction between the two Na + transport mechanisms. I Na-K was isolated as an external K + -induced current, and I Na-Ca as an external Ca 2+ - induced or Ni 2+ -sensitive current. The experimental protocol used for one ion carrier did not affect the other. The amplitude of I Na-K decreased to 54 ± 17 % of the initial peak during continuous application of K + with 20 mM Na + in the pipette. The outward I Na-Ca , which was intermittently activated by brief applications of Ca 2+ , decreased during activation of I Na-K , and recovered after cessation of I Na-K activation. These findings revealed a dynamic interaction between I Na-K and I Na-Ca via a depletion of Na + under the sarcolemma. To estimate changes in Na + concentration ([Na + ] i ) under the sarcolemma, the reversal potential ( V rev ) of I Na-Ca was measured. Unexpectedly, V rev hardly changed during activation of I Na-K . However, when I Na-Ca was blocked by Ni 2+ at the same time that I Na-K was activated, V rev changed markedly, maximally by +100 mV, immediately after the removal of Ni 2+ and K + . Subsarcolemmal [Na + ] i was calculated from the V rev of I Na-Ca on the assumption that the subsarcolemmal Ca 2+ concentration ([Ca 2+ ] i ) was fixed with EGTA, and mean [Na + ] i was calculated from both the time integral of I Na-K and the cell volume. The subsarcolemmal [Na + ] i was about seven times greater than the mean [Na + ] i . The interaction between the Na + -K + pump and Na + -Ca 2+ exchange was well simulated by a diffusion model, in which Na + diffusion was restricted to one-seventh (14 %) of the total cell volume.