A WB 4101-sensitive alpha-1 adrenergic receptor subtype modulates repolarization in canine Purkinje fibers.
We used standard microelectrode techniques to study alpha-1 adrenergic modulation of repolarization in canine Purkinje fibers. Our objectives were to subtype this alpha-1 receptor response pharmacologically, to determine whether alpha-1 adrenergic modulation of repolarization is dependent on the function of a pertussis toxin-sensitive G protein and to identify developmental changes in this alpha-1 response. Phenylephrine (Phe) induced a dose-dependent increase in transmembrane action potential duration at 50% (APD50) and 90% (APD90) repolarization. For the adult fibers, control APD50 and APD90 were 310 +/- 5 and 407 +/- 5 msec; after superfusion with Phe, 1 x 10(-6) M, the values were 350 +/- 6 and 468 +/- 8 msec, respectively (P less than .05). In 2- to 3-week-old dogs, control APD50 and APD90 were 170 +/- 14 and 255 +/- 10 msec; after superfusion with Phe, the values were 228 +/- 10 and 305 +/- 16 msec, respectively (P less than .05). Propranolol, 2 x 10(-7) M, did not affect the response to Phe. The alpha-1 blocker prazosin, 1 x 10(-7) M, and the alpha-1 receptor subtype selective antagonist, WB 4101, 1 x 10(-7) M, suppressed the response to Phe, but no effect on the response to Phe was seen with the subtype selective antagonist, chloroethylclonidine. In vivo pretreatment of dogs with pertussis toxin, 30 micrograms/kg i.v., decreased markedly the amount of G protein substrate available for subsequent in vitro ADP-ribosylation by pertussis toxin and [32P]NAD (from 7039 +/- 713 to 537 +/- 50 fmol/mg of protein in adult fibers and from 1134 to 62 fmol/mg of proteins in pooled young fibers). Pertussis toxin pretreatment increased the Phe-induced prolongation of APD50 and APD90 in the young and adult fibers.(ABSTRACT TRUNCATED AT 250 WORDS)
Lee
J H
JH
Department of Pharmacology, Columbia University, College of Physicians and Surgeons, New York, New York.
Steinberg
S F
SF
Rosen
M R
MR
D000200:Action Potentials / Q000187:drug effects; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D004146:Dioxanes / Q000494:pharmacology*; D004285:Dogs; D037342:Pertussis Toxin; D010656:Phenylephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000502:physiology; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D011942:Receptors, Adrenergic, alpha; D010566:Virulence Factors, Bordetella; D010656:Phenylephrine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; D037342:Pertussis Toxin; D011493:Protein Kinase C