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Research ArticleCARDIOVASCULAR

Comparison of L-Type Calcium Channel Blockade by Nifedipine and/or Cadmium in Guinea Pig Ventricular Myocytes

Jian-Bing Shen, Bin Jiang and Achilles J. Pappano
Journal of Pharmacology and Experimental Therapeutics August 2000, 294 (2) 562-570;
Jian-Bing Shen
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Bin Jiang
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Achilles J. Pappano
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Abstract

We tested the assumption that nifedipine blocks L-type calcium current [ICa(L)] at +10 mV and unmasks Na+/Ca2+ exchange-triggered contractions in guinea pig isolated ventricular myocytes. Voltage-clamp pulses elicited ICa(L) at +10 mV and evoked contractions in myocytes superfused with Tyrode's solution (35°C). Nifedipine blocked ICa(L) with an IC50 of 0.3 μM; this decreased to 50 nM at a holding potential of −40 mV, indicating preferential block of inactivated L-type Ca2+ channels. Use-independent block ofICa(L) increased with concentration (10–100 μM) and application time when nifedipine was rapidly applied (t1/2 = ∼0.2 s) during rest intervals (5–30 s). The fraction of use-dependent block ofICa(L) diminished with increasing drug concentration. Nifedipine also acceleratedICa(L) inactivation on the first test pulse. The combination of 30 μM nifedipine/30 μM Cd2+ (Nif 30/Cd 30) was as effective as 100 μM nifedipine to suppressICa(L) on the first test pulse at +10 mV. The incidence of complete block of contractions, as for complete block of ICa(L), increased as a function of nifedipine concentration and application time. Neither nifedipine nor Nif 30/Cd 30 affected Na+/Ca2+ exchange current at +10 to +100 mV. Contractions at +100 mV, although as large as those at +10 mV, were delayed in onset and resistant to nifedipine or Nif 30/Cd 30. We conclude that nifedipine-sensitiveICa(L) triggers contractions at +10 mV, whereas nifedipine-resistant Na+/Ca2+ exchange current initiates those at +100 mV.

Footnotes

  • Send reprint requests to: Achilles J. Pappano, Ph.D., Department of Pharmacology, MC-6125, University of Connecticut Health Center, 263 Farmington Ave., Farmington, CT 06030. E-mail:pappano{at}nso1.uchc.edu

  • ↵1 This study was supported by U.S. Public Health Service Grant HL-13339.

  • Abbreviations:
    CICR
    calcium-induced calcium release
    SR
    sarcoplasmic reticulum
    ICa(L)
    L-type calcium channel current
    ICa(T)
    T-type Ca2+ channel current
    INa/Ca
    Na+/Ca2+ exchange current
    DHP
    dihydropyridine
    Nif 30/Cd 30
    30 μM nifedipine plus 30 μM Cd2+
    E-C
    excitation-contraction
    • Received November 24, 1999.
    • Accepted April 14, 2000.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 294 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 294, Issue 2
1 Aug 2000
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Research ArticleCARDIOVASCULAR

Comparison of L-Type Calcium Channel Blockade by Nifedipine and/or Cadmium in Guinea Pig Ventricular Myocytes

Jian-Bing Shen, Bin Jiang and Achilles J. Pappano
Journal of Pharmacology and Experimental Therapeutics August 1, 2000, 294 (2) 562-570;

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Research ArticleCARDIOVASCULAR

Comparison of L-Type Calcium Channel Blockade by Nifedipine and/or Cadmium in Guinea Pig Ventricular Myocytes

Jian-Bing Shen, Bin Jiang and Achilles J. Pappano
Journal of Pharmacology and Experimental Therapeutics August 1, 2000, 294 (2) 562-570;
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