Details

Autor(en) / Beteiligte

• Williams, David L.
• Katz, George M.
• Roy-Contancin, Lydie
• Reuben, John P.

Titel

Guanosine 5′-monophosphate Modulates Gating of High-Conductance Ca2+-Activated K+ Channels in Vascular Smooth Muscle Cells

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 1988-12, Vol.85 (23), p.9360-9364

Ort / Verlag

Washington, DC: National Academy of Sciences of the United States of America

Erscheinungsjahr

1988

Quelle

MEDLINE

Beschreibungen/Notizen

• Ca2+-activated K+ channels (PKCa channels) account for the predominant K+ permeability of many types of smooth muscle cells. When activated, they oppose depolarization due to Na+ and Ca2+ channel activity. Several vasodilatory agents that increase intracellular cGMP levels (e.g., nitropruside, adenosine, and atrial natriuretic factor) enhance the activity of these high-conductance PKCa channels in on-cell patches of bovine aortic smooth muscle cells. In addition, dibutyryl-cGMP (1.0 mM) causes a similar increase in channel activity. To purpose the mechanism of channel modulation by these agents, a series of guanine and adenine nucleotides were evaluated by using inside-out excised patches. Whereas cAMP, AMP, ADP, and ATP were ineffective, all of the corresponding guanine nucleotides potentiated PKCa channel activity when tested at a high concentration (500 μ M). However, only GMP consistently enhanced channel activity in the 1-100 μ M range by increasing the percent open time and frequency of opening of these channels over a wide range of potentials and Ca2+ levels without affecting single-channel conductance. Thus, GMP is a potent modulator of PKCa channels and it, rather than cGMP, may mediate the action of the vasodilators examined in this study.