Biomaterial Database

Effect of anoxic preconditioning on ATP-sensitive potassium channels in guinea-pig ventricular myocytes. 2000

Z Zhu, and Y L Li, and D P Li, and R R He

Department of Physiology, Institute of Basic Medicine, Hebei Medical University, Shijiazhuang, People's Republic of China.

Ischemic or hypoxic preconditioning in experimental animals and humans is described. The mechanism of preconditioning may involve several endogenous substances released from ischemic or hypoxic tissues (such as adenosine, noradrenaline and bradykinin) that stimulate protein kinase C (PKC), which then phosphorylates ATP-sensitive potassium channels (K(ATP) channels). However, the effect of hypoxic preconditioning on K(ATP) channels in guinea-pig ventricular myocytes is unclear. The uncoupler carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) has been shown to activate K(ATP) channels in isolated cardiac cells. In the present study we tested whether anoxic preconditioning (APC) could affect the opening of K(ATP) channels activated by metabolic inhibition (MI) induced by FCCP in cell-attached and inside-out patches from guinea-pig ventricular myocytes. We measured the channel activity as NP(o)i and calculated it using the formula Po=I/(Ni), where Po is open-state probability, I is the mean patch current carried by all K(ATP) channels activated in a particular patch for a certain period of time, N is the number of functioning channels in the patch, and i is the unitary current of the K(ATP) channels. In cell-attached membrane patches, after about 5 min of initiating MI, K(ATP) channels were activated at a holding potential of +40 mV (NP(o)i=3.70+/-0.9 pA); APC pretreatment (3 min of anoxia followed by 7 min of reoxygenation) before MI (APC+MI group) shortened the time to activate K(ATP) channels by MI (2.3+/-0.5 min) and increased the activity of K(ATP)currents (NP(o)i=8.4+/-0.5 pA). This effect of APC was eliminated by administration of a PKC blocker, chelerythrine (5 microM), for 5 min before the APC pretreatment. In the inside-out patches, the IC50 of intracellular ATP against the K(ATP) channels in the APC+MI group was significantly increased to 642 microM compared to that in the MI group (IC50 of intracellular ATP =252 microM). Chelerythrine inhibited the effect of APC on the sensitivity of K(ATP) channels to the intracellular ATP concentration (IC50 of [ATP]i=301 microM). Our results demonstrate that APC can increase and accelerate the opening of K(ATP) channels induced by MI, and decrease the sensitivity of K(ATP) channels to [ATP]i, which is mediated by promoting the activation of PKC induced by APC.

UI	MeSH Term	Description	Entries
D007425	Intracellular Membranes	Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES.	Membranes, Intracellular,Intracellular Membrane,Membrane, Intracellular
D009206	Myocardium	The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.	Muscle, Cardiac,Muscle, Heart,Cardiac Muscle,Myocardia,Cardiac Muscles,Heart Muscle,Heart Muscles,Muscles, Cardiac,Muscles, Heart
D010617	Phenanthridines
D011493	Protein Kinase C	An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.	Calcium Phospholipid-Dependent Protein Kinase,Calcium-Activated Phospholipid-Dependent Kinase,PKC Serine-Threonine Kinase,Phospholipid-Sensitive Calcium-Dependent Protein Kinase,Protein Kinase M,Calcium Activated Phospholipid Dependent Kinase,Calcium Phospholipid Dependent Protein Kinase,PKC Serine Threonine Kinase,Phospholipid Sensitive Calcium Dependent Protein Kinase,Phospholipid-Dependent Kinase, Calcium-Activated,Serine-Threonine Kinase, PKC
D002259	Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone	A proton ionophore that is commonly used as an uncoupling agent in biochemical studies.	Carbonyl Cyanide para-Trifluoromethoxyphenylhydrazone,FCCP,(4-(Trifluoromethoxy)phenyl)hydrazonopropanedinitrile,Carbonyl Cyanide p Trifluoromethoxyphenylhydrazone,Carbonyl Cyanide para Trifluoromethoxyphenylhydrazone,Cyanide p-Trifluoromethoxyphenylhydrazone, Carbonyl,Cyanide para-Trifluoromethoxyphenylhydrazone, Carbonyl,p-Trifluoromethoxyphenylhydrazone, Carbonyl Cyanide,para-Trifluoromethoxyphenylhydrazone, Carbonyl Cyanide
D004594	Electrophysiology	The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.
D004791	Enzyme Inhibitors	Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.	Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006168	Guinea Pigs	A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.	Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006352	Heart Ventricles	The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation.	Cardiac Ventricle,Cardiac Ventricles,Heart Ventricle,Left Ventricle,Right Ventricle,Left Ventricles,Right Ventricles,Ventricle, Cardiac,Ventricle, Heart,Ventricle, Left,Ventricle, Right,Ventricles, Cardiac,Ventricles, Heart,Ventricles, Left,Ventricles, Right
D000255	Adenosine Triphosphate	An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.	ATP,Adenosine Triphosphate, Calcium Salt,Adenosine Triphosphate, Chromium Salt,Adenosine Triphosphate, Magnesium Salt,Adenosine Triphosphate, Manganese Salt,Adenylpyrophosphate,CaATP,CrATP,Manganese Adenosine Triphosphate,MgATP,MnATP,ATP-MgCl2,Adenosine Triphosphate, Chromium Ammonium Salt,Adenosine Triphosphate, Magnesium Chloride,Atriphos,Chromium Adenosine Triphosphate,Cr(H2O)4 ATP,Magnesium Adenosine Triphosphate,Striadyne,ATP MgCl2