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1H, a cloned human T-type
calcium channel
1 Department of Physiology, The University of Kentucky College of Medicine, Lexington, Kentucky 40536-0298; and 2 Department of Physiology and Cardiovascular Institute, Loyola University Medical Center, Maywood, Illinois 60153
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, 
1H, is modulated by external AA. AA (10 µM) causes a
slow, time-dependent attenuation of 1H current. At a holding potential of 
80 mV, 10 µM AA reduces peak inward 1H 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
1H. The epoxygenase metabolite epoxyeicosatrienoic acid
(8,9-EET) mimicked the inhibitory effect of AA on 1H peak current. A
protein kinase C (PKC)-specific inhibitor (peptide fragment 19-36)
only partially antagonized the AA-induced reduction of peak 1H
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 1H. These results suggest that AA
attenuation and shift of 1H 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.
low-voltage-activated calcium channel; epoxyeicosatrienoic acid; cardiac; window current
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