Biomaterial Database

Modulation of delayed afterdepolarisations by alpha 1 adrenergic receptor subtypes. 1993

J H Lee, and M R Rosen

Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.

OBJECTIVE The aim was to evaluate the role of alpha 1 adrenoceptor stimulation and selective receptor subtype blockade on delayed afterdepolarisations induced by high extracellular calcium ([Ca2+]o = 8.1 mM) and by ouabain (2 x 10(-7) M) in canine Purkinje fibres. METHODS Standard microelectrode techniques were used to record transmembrane action potentials from Purkinje fibres placed at cycle length = 500 ms. The drive was interrupted for 5 s every minute to allow observation of delayed afterdepolarisations or any subsequent spontaneous rhythms. RESULTS The alpha 1 adrenoceptor agonist phenylephrine, 1 x 10(-7) M, increased the amplitude of delayed afterdepolarisations induced by high [Ca] from 4.2(SEM 0.4) to 5.4(0.2) mV (p < 0.05), and by ouabain from 4.3(0.6) to 6.9(1.0) mV (p < 0.05). The selective alpha 1 adrenoceptor subtype agonist WB 4101, 1 x 10(-7) M, blocked the effect of phenylephrine on delayed afterdepolarisations induced by ouabain + phenylephrine [DAD = 4.6(0.6), p < 0.05] but decreased the amplitude of those induced by Ca + phenylephrine, to 2.0(0.3) mV (p < 0.05). In contrast, the selective alpha 1b adrenoceptor antagonist chloroethylclonidine, 1 x 10(-7) M, increased the amplitude of delayed afterdepolarisations induced by Ca and phenylephrine to 6.6(0.6) mV (p < 0.05) and by ouabain and phenylephrine to 12.6(2.0) mV (p < 0.05). CONCLUSIONS alpha 1 Adrenoceptor subtypes modulate the amplitude of delayed afterdepolarisations induced by ouabain and by high [Ca]. The chloroethylclonidine-blocked alpha 1 adrenoceptor subtype decreases, and the WB 4101-blocked subtype potentiates, this arrhythmogenic mechanism.

UI	MeSH Term	Description	Entries
D010042	Ouabain	A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like DIGITALIS. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-EXCHANGING ATPASE.	Acocantherin,G-Strophanthin,Acolongifloroside K,G Strophanthin
D010656	Phenylephrine	An alpha-1 adrenergic agonist used as a mydriatic, nasal decongestant, and cardiotonic agent.	(R)-3-Hydroxy-alpha-((methylamino)methyl)benzenemethanol,Metaoxedrin,Metasympatol,Mezaton,Neo-Synephrine,Neosynephrine,Phenylephrine Hydrochloride,Phenylephrine Tannate,Neo Synephrine,Tannate, Phenylephrine
D011690	Purkinje Fibers	Modified cardiac muscle fibers composing the terminal portion of the heart conduction system.	Purkinje Fiber,Fiber, Purkinje,Fibers, Purkinje
D011942	Receptors, Adrenergic, alpha	One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation.	Adrenergic alpha-Receptor,Adrenergic alpha-Receptors,Receptors, alpha-Adrenergic,alpha-Adrenergic Receptor,alpha-Adrenergic Receptors,Receptor, Adrenergic, alpha,Adrenergic alpha Receptor,Adrenergic alpha Receptors,Receptor, alpha-Adrenergic,Receptors, alpha Adrenergic,alpha Adrenergic Receptor,alpha Adrenergic Receptors,alpha-Receptor, Adrenergic,alpha-Receptors, Adrenergic
D002118	Calcium	A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.	Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D003000	Clonidine	An imidazoline sympatholytic agent that stimulates ALPHA-2 ADRENERGIC RECEPTORS and central IMIDAZOLINE RECEPTORS. It is commonly used in the management of HYPERTENSION.	Catapres,Catapresan,Catapressan,Chlophazolin,Clofelin,Clofenil,Clonidine Dihydrochloride,Clonidine Hydrochloride,Clonidine Monohydrobromide,Clonidine Monohydrochloride,Clopheline,Dixarit,Gemiton,Hemiton,Isoglaucon,Klofelin,Klofenil,M-5041T,ST-155,Dihydrochloride, Clonidine,Hydrochloride, Clonidine,M 5041T,M5041T,Monohydrobromide, Clonidine,Monohydrochloride, Clonidine,ST 155,ST155
D004146	Dioxanes	Compounds that contain the structure 1,4-dioxane.
D004285	Dogs	The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)	Canis familiaris,Dog
D006321	Heart	The hollow, muscular organ that maintains the circulation of the blood.	Hearts
D000200	Action Potentials	Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.	Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential