J H Lee1, M R Rosen. 1. Department of Pharmacology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
Abstract
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.
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.
Authors: Karolina Pytka; Klaudia Lustyk; Elżbieta Żmudzka; Magdalena Kotańska; Agata Siwek; Małgorzata Zygmunt; Agnieszka Dziedziczak; Joanna Śniecikowska; Adrian Olczyk; Adam Gałuszka; Jarosław Śmieja; Anna M Waszkielewicz; Henryk Marona; Barbara Filipek; Jacek Sapa; Szczepan Mogilski Journal: Front Pharmacol Date: 2016-08-03 Impact factor: 5.810