Two pathways for Ca2+ channel gating differentially modulated by physiological stimuli

S. Richard, F. Tiaho, P. Charnet, J. Nargeot, J. M. Nerbonne

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37 Scopus citations

Abstract

In cardiac muscle, Ca2+ entry through voltage-gated Ca2+ channels plays an important role in the generation of action potentials and in the development of tension. Although it had been assumed that there was a single type of cardiac Ca2+ channel, recent studies reveal that multiple Ca2+ channel types coexist in some myocardial cells. Here, we report that macroscopic Ca2+ current (I(Ca)) waveforms in isolated adult rat ventricular myocytes comprise two kinetically distinct components; these are referred to here as I(Ca)(fc) and I(Ca)(sc) to denote the fast and slow components, respectively, of I(Ca) decay. In contrast to findings in other cells, the properties of I(Ca)(fc) and I(Ca)(sc) suggest the presence of two pathways for gating of a single type of high-threshold Ca2+ channel rather than two distinct Ca2+ channel types. In addition, gating via I(Ca)(fc) and I(Ca)(sc) is regulated by changes in membrane potential and stimulation frequency. Hyperpolarized potentials and low stimulation frequencies reveal preferential activation via I(Ca)(fc); depolarized potentials and high stimulation frequencies, in contrast, favor activation via I(Ca)(sc). After exposure to β-adrenergic agonists or the Ca2+ agonist BAY K 8644, peak I(Ca) amplitudes increase owing to the preferential augmentation of I(Ca)(fc); β-agonists and BAY K 8644 also increase I(Ca)(sc), albeit to a smaller extent than I(Ca)(fc). Thus, in addition to voltage- and frequency-dependent regulation, the two pathways for Ca2+ channel gating are modulated differentially by β-adrenergic and Ca2+ channel agonists.

Original languageEnglish
Pages (from-to)H1872-H1881
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume258
Issue number6 27-6
StatePublished - Aug 2 1990

Keywords

  • BAY K 8644
  • L-type calcium channels
  • cardiac calcium channels
  • dihydropyridine effects on calcium channel gating
  • high-voltage activated calcium channels
  • isoprenaline
  • β-adrenergic modulation of calcium channel gating

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