Ion-dependent inactivation of barium current through L-type calcium channels

Gonzalo Ferreira, Jianxun Yi, Eduardo Ríos, Roman Shirokov

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Abstract

It is widely believed that Ba2+ currents carried through L-type Ca2+ channels inactive by a voltage-dependent mechanism similar to that described for other voltage-dependent channels. Studying ionic and gating currents of rabbit cardiac Ca2+ channels expressed in different subunit combinations in tsA201 cells, we found a phase of Ba2+ current decay with characteristics of ion-dependent inactivation. Upon a long duration (20 s) depolarizing pulse, I(Ba) decayed as the sum of two exponentials. The slow phase (τ ≃ 6 s, 21°C) was parallel to a reduction of gating charge mobile at positive voltages, which was determined in the same cells. The fast phase of current decay (τ ≃ 600 ms), involving about 50% of total decay, was not accompanied by decrease of gating currents. Its amplitude depended on voltage with a characteristic U-shape, reflecting reduction of inactivation at positive voltages. When Na+ was used as the charge carrier, decay of ionic current followed a single exponential, of rate similar to that of the slow decay of Ba2+ current. The reduction of Ba2+ current during a depolarizing pulse was not due to changes in the concentration gradients driving ion movement, because Ba2+ entry during the pulse did not change the reversal potential for Ba2+. A simple model of Ca2+-dependent inactivation (Shirokov, R., R. Levis, N. Shirokova, and E. Rios. 1993. J. Gen. Physiol. 102:1005-1030) robustly accounts for fast Ba2+ current decay assuming the affinity of the inactivation site on the α1 subunit to be 100 times lower for Ba2+ than Ca2+.

Original languageEnglish (US)
Pages (from-to)449-461
Number of pages13
JournalJournal of General Physiology
Volume109
Issue number4
DOIs
StatePublished - Apr 1997

All Science Journal Classification (ASJC) codes

  • Physiology

Keywords

  • cardiac muscle
  • gating current
  • heterologous expression
  • signal transduction

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