Arachidonic acid modulation of α1H, a cloned human T-type calcium channel

Y. Zhang, Leanne L. Cribbs, Jonathan Satin

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


Arachidonic acid (AA) and the products of its metabolism are central mediators of changes in cellular excitability. We show that the recently cloned and expressed T-type or low-voltage-activated Ca channel, α1H, is modulated by external AA. AA (10 μM) causes a slow, time-dependent attenuation of α1H current. At a holding potential of -80 mV, 10 μM AA reduces peak inward α1H current by 15% in 15 min and 70% in 30 min and shifts the steady-state inactivation curve -25 mV. AA inhibition was not affected by applying the cyclooxygenase inhibitor indomethacin or the lipoxygenase inhibitor nordihydroguaiaretic acid. The epoxygenase inhibitor octadecynoic acid partially antagonized AA attenuation of α1H. The epoxygenase metabolite epoxyeicosatrienoic acid (8,9-EET) mimicked the inhibitory effect of AA on α1H peak current. A protein kinase C (PKC)- specific inhibitor (peptide fragment 19-36) only partially antagonized the AA-induced reduction of peak α1H current and the shift of the steady-state inactivation curve but had no effect on 8,9-EET-induced attenuation of current. In contrast, PKA has no role in the modulation of α1H. These results suggest that AA attenuation and shift of α1H may be mediated directly by AA. The heterologous expression of T-type Ca channels allows us to study for the first time properties of this important class of ion channel in isolation. There is a significant overlap of the steady-state activation and inactivation curves, which implies a substantial window current. The selective shift of the steady-state inactivation curve by AA reduces peak Ca current and eliminates the window current. We conclude that AA may partly mediate physiological effects such as vasodilatation via the attenuation of T-type Ca channel current and the elimination of a T-type channel steady window current.

Original languageEnglish
Pages (from-to)H184-H193
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Issue number1 47-1
StatePublished - Jan 2000


  • Cardiac
  • Epoxyeicosatrienoic acid
  • Low-voltage-activated calcium channel
  • Window current

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)


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