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OtherCELLULAR AND MOLECULAR PHARMACOLOGY

Differential Electrophysiological Actions of Endothelin-1 on Cl– and K+ Currents in Myocytes Isolated from Aorta, Basilar and Pulmonary Artery

Katie J. Salter and Roland Z. Kozlowski
Journal of Pharmacology and Experimental Therapeutics March 1998, 284 (3) 1122-1131;
Katie J. Salter
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Roland Z. Kozlowski
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Abstract

The electrophysiological effects of endothelin (ET)-1 were compared in myocytes isolated from rat small pulmonary artery, basilar artery and aorta. ET-1 evoked depolarization in all three smooth muscle cell types. Depolarizing oscillations in membrane current also were observed in pulmonary and aortic myocytes. In voltage-clamp experiments ET-1 induced a gradual inhibition of the Ca++-independent outward current (IK) in pulmonary and aortic myocytes, whereas in basilar myocytes ET-1 inhibited the Ca++-activated K+ current (IK(Ca)). ET-1 also evoked a transient enhancement of IK(Ca) and oscillations in inward current in aortic and pulmonary myocytes. The inward currents were inhibited by caffeine, which suggests Ca++-dependent activation. Ion-exchange experiments indicated that in pulmonary myocytes oscillatory currents were caused solely by the movement of Cl−, whereas in aortic myocytes they were the consequence of both Ca++-activated Cl− (ICl(Ca)) and nonselective cation currents (INS). No inward current was evoked in basilar myocytes in response to ET-1 or photorelease of Ca++, which suggests that these cells do not possess ICl(Ca). Experiments with ET receptor ligands indicated that in basilar myocytes ETAreceptor stimulation is responsible for IK(Ca) inhibition, whereas in aortic and pulmonary myocytes ETB and ETA receptor stimulation mediates inhibition of IK and activation of ICl(Ca), INSand IK(Ca), respectively. In the future, it may be possible to exploit these differential effects of ET-1 pharmacologically to assist development of tissue-specific modulators for the treatment of vascular disease.

Footnotes

  • Send reprint requests to: Roland Z. Kozlowski, University Department of Pharmacology, Mansfield Road, Oxford, United Kingdom OX1 3QT.

  • ↵1 This research was supported by the British Heart Foundation, the Medical Research Council, the Royal Society and the Wellcome Trust (K.J.S. is a Wellcome Prize Student).

  • Abbreviations:
    ET
    endothelin
    [Ca++]i
    intracellular Ca++concentration
    HEPES
    N-[2-hydroxyethyl]piperazine-N′-[2-ethanesulfonic acid]
    IbTX
    iberiotoxin
    ICl(Ca)
    Ca++-activated Cl− current
    IK
    K+ current
    IK(Ca)
    Ca++-activated K+ current
    INS
    Ca++-dependent nonselective cation current
    IKV
    delayed-rectifying K+ current
    KCa channel
    Ca++-activated K+channel
    4-AP
    4-aminopyridine
    TEA
    tetraethylammonium
    EGTA
    ethylene glycol-bis(β-aminoethyl ether) N,N,N′,N′-tetraacetic acid
    STXS6c
    sarafotoxin S6c
    Nitr-5
    1-[2-amino-5-{1-hydroxy-1-[2-nitro-4,5-methylenedioxyphenyl] methyl} phenoxy]-2-{2′-amino-5′-methylphenoxy}ethane-N,N,N′,N′′-tetraacetic acid, sodium
    STOC
    spontaneous transient outward current
    • Received June 18, 1997.
    • Accepted November 17, 1997.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 284, Issue 3
1 Mar 1998
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OtherCELLULAR AND MOLECULAR PHARMACOLOGY

Differential Electrophysiological Actions of Endothelin-1 on Cl– and K+ Currents in Myocytes Isolated from Aorta, Basilar and Pulmonary Artery

Katie J. Salter and Roland Z. Kozlowski
Journal of Pharmacology and Experimental Therapeutics March 1, 1998, 284 (3) 1122-1131;

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OtherCELLULAR AND MOLECULAR PHARMACOLOGY

Differential Electrophysiological Actions of Endothelin-1 on Cl– and K+ Currents in Myocytes Isolated from Aorta, Basilar and Pulmonary Artery

Katie J. Salter and Roland Z. Kozlowski
Journal of Pharmacology and Experimental Therapeutics March 1, 1998, 284 (3) 1122-1131;
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