Modulation of delayed afterdepolarisations by alpha 1 adrenergic receptor subtypes.
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.
Lee
J H
JH
Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Rosen
M R
MR
D000200:Action Potentials / Q000187:drug effects; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D046508:Culture Techniques; D004146:Dioxanes / Q000494:pharmacology; D004285:Dogs; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D010042:Ouabain / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011690:Purkinje Fibers / Q000502:physiology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; D010656:Phenylephrine; C051731:chlorethylclonidine; D010042:Ouabain; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D003000:Clonidine; D002118:Calcium