TY - JOUR
T1 - Adenosine triphosphate-sensitive potassium channels in the cardiovascular system
AU - Nichols, C. G.
AU - Lederer, W. J.
PY - 1991
Y1 - 1991
N2 - ATP is normally available in cells at millimolar concentrations and is ''buffered'' by intracellular pools of other high-energy phosphates, such as creatine phosphate. Thus intracellular [ATP] ([ATP](i)) may seem an unlikely candidate for a regulatory signal inside cells. Recent evidence suggests, however, that [ATP](i) regulates the behavior of a class of potassium (K(ATP)) channels that are found throughout the cardiovascular system. K(ATP) channels are present in cardiac, skeletal, and vascular smooth muscle. The channels are inhibited by micromolar [ATP](i), and this inhibition is relieved by micromolar [ADP](i). We present evidence in support of the idea that variations of [ATP](i) and [ADP](i), even within normal concentration ranges, may influence cellular function in the heart and vascular system via a direct action on the K(ATP) channel. Furthermore, very specific modulators of K(ATP) channel activity are available. We discuss the mechanism of action of these agents and their interaction with endogenous modulators and consider their potential roles in cardiovascular therapy.
AB - ATP is normally available in cells at millimolar concentrations and is ''buffered'' by intracellular pools of other high-energy phosphates, such as creatine phosphate. Thus intracellular [ATP] ([ATP](i)) may seem an unlikely candidate for a regulatory signal inside cells. Recent evidence suggests, however, that [ATP](i) regulates the behavior of a class of potassium (K(ATP)) channels that are found throughout the cardiovascular system. K(ATP) channels are present in cardiac, skeletal, and vascular smooth muscle. The channels are inhibited by micromolar [ATP](i), and this inhibition is relieved by micromolar [ADP](i). We present evidence in support of the idea that variations of [ATP](i) and [ADP](i), even within normal concentration ranges, may influence cellular function in the heart and vascular system via a direct action on the K(ATP) channel. Furthermore, very specific modulators of K(ATP) channel activity are available. We discuss the mechanism of action of these agents and their interaction with endogenous modulators and consider their potential roles in cardiovascular therapy.
KW - Action potential
KW - Adenosine diphosphate
KW - Heart
KW - Metabolism
KW - Potassium channel opener
KW - Sulfonylurea
UR - http://www.scopus.com/inward/record.url?scp=0026344826&partnerID=8YFLogxK
U2 - 10.1152/ajpheart.1991.261.6.h1675
DO - 10.1152/ajpheart.1991.261.6.h1675
M3 - Review article
C2 - 1750525
AN - SCOPUS:0026344826
SN - 0002-9513
VL - 261
SP - H1675-H1686
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 6 30-6
ER -