Block of the background K+ channel TASK-1 contributes to arrhythmogenic effects of platelet-activating factor
Articolo
Data di Pubblicazione:
2002
Citazione:
Block of the background K+ channel TASK-1 contributes to arrhythmogenic effects of platelet-activating factor / A. Barbuti, S. Ishii, T. Shimizu, R.B. Robinson, S.J. Feinmark. - In: AMERICAN JOURNAL OF PHYSIOLOGY. HEART AND CIRCULATORY PHYSIOLOGY. - ISSN 0363-6135. - 282:6(2002 Jun), pp. H2024-H2030.
Abstract:
Platelet-activating factor (PAF), an inflammatory phospholipid, induces ventricular arrhythmia via an unknown ionic mechanism. We can now link PAF-mediated cardiac electrophysiological effects to inhibition of a two-pore domain K(+) channel [TWIK-related acid-sensitive K(+) background channel (TASK-1)]. Superfusion of carbamyl-PAF (C-PAF), a stable analog of PAF, over murine ventricular myocytes causes abnormal automaticity, plateau phase arrest of the action potential, and early afterdepolarizations in paced and quiescent cells from wild-type but not PAF receptor knockout mice. C-PAF-dependent currents are insensitive to Cs(+) and are outwardly rectifying with biophysical properties consistent with a K(+)-selective channel. The current is blocked by TASK-1 inhibitors, including protons, Ba(2+), Zn(2+), and methanandamide, a stable analog of the endogenous lipid ligand of cannabinoid receptors. In addition, when TASK-1 is expressed in CHO cells that express an endogenous PAF receptor, superfusion of C-PAF decreases the expressed current. Like C-PAF, methanandamide evoked spontaneous activity in quiescent myocytes. C-PAF- and methanandamide-sensitive currents are blocked by a specific protein kinase C (PKC) inhibitor, implying overlapping signaling pathways. In conclusion, C-PAF blocks TASK-1 or a closely related channel, the effect is PKC dependent, and the inhibition alters the electrical activity of myocytes in ways that would be arrhythmogenic in the intact heart
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
two-pore domain potassium channels; Kcnk3 ventricular myocytes; inflammatory lipids; mouse
Elenco autori:
A. Barbuti, S. Ishii, T. Shimizu, R.B. Robinson, S.J. Feinmark
Link alla scheda completa: