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Responses to Norepinephrine of Normal and “Ischemic” Canine Purkinje Fibers are Consistent with Activation of Different α 1 ‐Receptor Subtypes
Author(s) -
ANYUKHOVSKY EVGENY P.,
GUO SHIDUO,
DANILO PETER,
ROSEN MICHAEL R.
Publication year - 1997
Publication title -
journal of cardiovascular electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.193
H-Index - 138
eISSN - 1540-8167
pISSN - 1045-3873
DOI - 10.1111/j.1540-8167.1997.tb01829.x
Subject(s) - medicine , norepinephrine , cardiology , purkinje fibers , receptor , endocrinology , neuroscience , electrophysiology , dopamine , biology
α 1 ‐Receptor Subtype Stimulation of Purkinje Fibers. Introduction: Previously we found that WB4101 (WB) 10 ‐7 M competitively blocks three α 1 ‐adrenergic receptor‐effector responses: the increase in normal automaticity occurring in Purkinje fibers (PF) at high membrane potentials: the increase in abnormal automaticity occurring in PF at depolarized membrane potentials; and the prolongation of PF action potential duration. These observations are consistent with two different hypotheses: (1) WB blocks a single α 1 ‐receptor subtype, which subserves different effector pathways; and (2) WB blocks different receptor subtypes, eacb of which subserves an independent patbway. The aim of this study was to test both hypotheses. Methods and Results: We used standard microelectrode techniques to study the concentration‐dependent actions of three α 1 ‐adrenoreceptor blockers (WB (α 1A ≫α 1D ], 5‐methylurapidil [5‐MU] [α 1A , ≫α 1D ], and UK52,046 [nonselective]) on norepinephrine (NK) effects in normal PF and in PF depolarized with a simulated ischemic solution ([K + ] o = 10 mM; pO 2 < 20 mmHg; pH 6.8; maximum diastolic potential ‐60 ± 1 mV). In normally polarized PF, concentration‐dependent actions of all blockers on both the positive cbronotropic response and the prolongation of action potential duration completely coincide. In contrast, the response to NE of abnormal automaticity in “ischemic” PF differs from normals: there is a bigh sensitivity to WB and 5‐MU and no response to UK52,046. Conclusions: (1) A single receptor subtype appears responsible for botb the α 1 ‐induced prolongation of repolarization and the positive chronotropic effect in normal PF. (2) Two different receptor subtypes may be responsible for the α 1 ‐induced effects on automaticity in normal and ischemic fibers. It is likely that the latter one is α 1A , and that consideration of antiarrhythmic therapy with α 1 ‐adrenergic blockers should focus on this subtype as a potential target.