Biomaterial Database

Phosphorylation by protein kinase A enhances delayed rectifier K+ current in rabbit vascular smooth muscle cells. 1995

E A Aiello, and M P Walsh, and W C Cole

Smooth Muscle Research Group, Faculty of Medicine, University of Calgary, Alberta, Canada.

The effect of adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA) activity on 4-aminopyridine (4-AP)-sensitive delayed rectifier current (IdK) in isolated rabbit portal vein smooth muscle cells was studied via whole cell voltage clamp (20-22 degrees C). A threefold increase in 4-AP-sensitive (5 mM) IdK was recorded after gaining cell access during dialysis with 5 mM intracellular ATP and internal Ca2+ buffered to a low level with 5 mM ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. Dialysis with the nonhydrolyzable ATP analogue 5'-adenylylimidodiphosphate (5 mM) or the specific peptide inhibitor of PKA (PKI; 10 microM) reduced current runup by 50 and 70%, respectively. Delayed dialysis with PKI reversed runup and inhibited IdK to below initial levels. Forskolin (1 microM) caused a reversible increase in IdK, which was inhibited by 4-AP (5 mM). Isoproterenol (1 microM) reversibly enhanced IdK; the increase was sensitive to propranolol (2 microM) and 4-AP (5 mM) and was prevented by dialysis with PKI (10 microM). IdK was enhanced over the entire voltage range of activation and associated with a negative shift in reversal potential of net whole cell current, consistent with hyperpolarization of resting membrane potential. The data provide the first evidence for a signal transduction mechanism involving beta-adrenoceptors, adenylate cyclase, and a phosphotransferase reaction mediated by PKA for the regulation of delayed rectifier K+ channels in vascular smooth muscle.

UI	MeSH Term	Description	Entries
D007545	Isoproterenol	Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.	Isoprenaline,Isopropylarterenol,4-(1-Hydroxy-2-((1-methylethyl)amino)ethyl)-1,2-benzenediol,Euspiran,Isadrin,Isadrine,Isopropyl Noradrenaline,Isopropylnoradrenaline,Isopropylnorepinephrine,Isoproterenol Hydrochloride,Isoproterenol Sulfate,Isuprel,Izadrin,Norisodrine,Novodrin,Hydrochloride, Isoproterenol,Noradrenaline, Isopropyl,Sulfate, Isoproterenol
D009131	Muscle, Smooth, Vascular	The nonstriated involuntary muscle tissue of blood vessels.	Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D010766	Phosphorylation	The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.	Phosphorylations
D011188	Potassium	An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.
D011817	Rabbits	A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes.	Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D002469	Cell Separation	Techniques for separating distinct populations of cells.	Cell Isolation,Cell Segregation,Isolation, Cell,Cell Isolations,Cell Segregations,Cell Separations,Isolations, Cell,Segregation, Cell,Segregations, Cell,Separation, Cell,Separations, Cell
D005576	Colforsin	Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.	Coleonol,Forskolin,N,N-Dimethyl-beta-alanine-5-(acetyloxy)-3-ethenyldodecahydro-10,10b-dihydroxy-3,4a,7,7,10a-pentamethyl-1-oxo-1H-naphtho(2,1-b)pyran-6-yl Ester HCl,NKH 477,NKH-477,NKH477
D000266	Adenylyl Imidodiphosphate	5'-Adenylic acid, monoanhydride with imidodiphosphoric acid. An analog of ATP, in which the oxygen atom bridging the beta to the gamma phosphate is replaced by a nitrogen atom. It is a potent competitive inhibitor of soluble and membrane-bound mitochondrial ATPase and also inhibits ATP-dependent reactions of oxidative phosphorylation.	Adenyl Imidodiphosphate,gamma-Imino-ATP,AMP-PNP,AMPPNP,ATP(beta,gamma-NH),Adenosine 5'-(beta,gamma-Imino)triphosphate,Adenylimidodiphosphate,Adenylylimidodiphosphate,Mg AMP-PNP,Mg-5'-Adenylylimidodiphosphate,beta,gamma-imido-ATP,gamma-Imido-ATP,AMP-PNP, Mg,Imidodiphosphate, Adenyl,Imidodiphosphate, Adenylyl,Mg 5' Adenylylimidodiphosphate,Mg AMP PNP,beta,gamma imido ATP,gamma Imido ATP,gamma Imino ATP
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D015761	4-Aminopyridine	One of the POTASSIUM CHANNEL BLOCKERS with secondary effect on calcium currents which is used mainly as a research tool and to characterize channel subtypes.	4-Aminopyridine Sustained Release,Dalfampridine,Fampridine-SR,Pymadine,VMI-103,4 Aminopyridine,4 Aminopyridine Sustained Release,Fampridine SR,Sustained Release, 4-Aminopyridine,VMI 103,VMI103