Electrophysiological effects of α2-adrenergic stimulation in canine cardiac Purkinje fibers

Ricardo A Samson, J. J. Cai, E. F. Shibata, J. B. Martins, H. C. Lee

Research output: Contribution to journalArticle

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Abstract

The effects of α2-adrenergic stimulation on action potentials were measured in isolated canine Purkinje fibers. Action potential durations at 50 and 90% of repolarization (APD50 and APD90) were significantly prolonged by 0.25 μM l-norepinephrine + 0.5 μM dl-propranolol (NE + P) from baseline values of 165 ± 7 and 249 ± 9 (SE) ms (n = 7) to 174 ± 7 and 265 ± 9 ms, respectively (P < 0.05 for both). Selective α2-blockade with 0.01 μM yohimbine (YO) reduced this prolongation by NE + P in APD50 and APD90 to 169 ± 7 and 256 ± 8 ms, respectively (P < 0.05 compared with NE + P). Additional selective α1-blockade with 0.01 μM prazosin (PZ) completely blocked the effects of NE + P, returning APD50 and APD90 to 163 ± 7 and 250 ± 9 ms (not different from baseline). After incubation of isolated Purkinje fibers with pertussis toxin (1 μg/ml), which reduced the availability of a 41-kDa membrane protein for ADP ribosylation by 70 ± 7% (n = 4, P < 0.05), YO failed to reverse the prolongation in action potential durations brought on by NE + P, but the effects of PZ were intact. The effects of α2-stimulation on β-adrenergic-induced delayed afterdepolarizations (DADs) were studied by burst pacing of Purkinje fibers in Tyrode solution containing 7.5 mM Ca2+. The DADs induced in the presence of NE + PZ (B- + α2-stimulation) were significantly smaller in amplitude and required a shorter pacing cycle length to reach threshold than those induced in the presence of NE + PZ + YO (unopposed β-adrenergic stimulation). Furthermore sustained triggered activity, seen in five of eight preparations under β-stimulation, could no longer be elicited in the presence of β- + α2-stimulation. These results suggest that the postjunctional α2-adrenergic receptors in canine Purkinje fibers are coupled to a pertussis toxin-sensitive G protein and that stimulation of these receptors leads to action potential prolongation and suppression of DADs induced by β-adrenergic stimulation.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume268
Issue number5 37-5
StatePublished - 1995
Externally publishedYes

Fingerprint

Purkinje Fibers
propranolol
norepinephrine
Propranolol
Adrenergic Agents
Prazosin
Canidae
Norepinephrine
action potentials
yohimbine
Action Potentials
Yohimbine
dogs
pertussis toxin
Pertussis Toxin
duration
adrenergic receptors
G-proteins
GTP-Binding Proteins
membrane proteins

Keywords

  • α-adrenergic receptor
  • action potential duration
  • delayed afterdepolarization
  • G protein
  • UK-14304

ASJC Scopus subject areas

  • Physiology
  • Agricultural and Biological Sciences(all)

Cite this

Electrophysiological effects of α2-adrenergic stimulation in canine cardiac Purkinje fibers. / Samson, Ricardo A; Cai, J. J.; Shibata, E. F.; Martins, J. B.; Lee, H. C.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 268, No. 5 37-5, 1995.

Research output: Contribution to journalArticle

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abstract = "The effects of α2-adrenergic stimulation on action potentials were measured in isolated canine Purkinje fibers. Action potential durations at 50 and 90{\%} of repolarization (APD50 and APD90) were significantly prolonged by 0.25 μM l-norepinephrine + 0.5 μM dl-propranolol (NE + P) from baseline values of 165 ± 7 and 249 ± 9 (SE) ms (n = 7) to 174 ± 7 and 265 ± 9 ms, respectively (P < 0.05 for both). Selective α2-blockade with 0.01 μM yohimbine (YO) reduced this prolongation by NE + P in APD50 and APD90 to 169 ± 7 and 256 ± 8 ms, respectively (P < 0.05 compared with NE + P). Additional selective α1-blockade with 0.01 μM prazosin (PZ) completely blocked the effects of NE + P, returning APD50 and APD90 to 163 ± 7 and 250 ± 9 ms (not different from baseline). After incubation of isolated Purkinje fibers with pertussis toxin (1 μg/ml), which reduced the availability of a 41-kDa membrane protein for ADP ribosylation by 70 ± 7{\%} (n = 4, P < 0.05), YO failed to reverse the prolongation in action potential durations brought on by NE + P, but the effects of PZ were intact. The effects of α2-stimulation on β-adrenergic-induced delayed afterdepolarizations (DADs) were studied by burst pacing of Purkinje fibers in Tyrode solution containing 7.5 mM Ca2+. The DADs induced in the presence of NE + PZ (B- + α2-stimulation) were significantly smaller in amplitude and required a shorter pacing cycle length to reach threshold than those induced in the presence of NE + PZ + YO (unopposed β-adrenergic stimulation). Furthermore sustained triggered activity, seen in five of eight preparations under β-stimulation, could no longer be elicited in the presence of β- + α2-stimulation. These results suggest that the postjunctional α2-adrenergic receptors in canine Purkinje fibers are coupled to a pertussis toxin-sensitive G protein and that stimulation of these receptors leads to action potential prolongation and suppression of DADs induced by β-adrenergic stimulation.",
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AU - Cai, J. J.

AU - Shibata, E. F.

AU - Martins, J. B.

AU - Lee, H. C.

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N2 - The effects of α2-adrenergic stimulation on action potentials were measured in isolated canine Purkinje fibers. Action potential durations at 50 and 90% of repolarization (APD50 and APD90) were significantly prolonged by 0.25 μM l-norepinephrine + 0.5 μM dl-propranolol (NE + P) from baseline values of 165 ± 7 and 249 ± 9 (SE) ms (n = 7) to 174 ± 7 and 265 ± 9 ms, respectively (P < 0.05 for both). Selective α2-blockade with 0.01 μM yohimbine (YO) reduced this prolongation by NE + P in APD50 and APD90 to 169 ± 7 and 256 ± 8 ms, respectively (P < 0.05 compared with NE + P). Additional selective α1-blockade with 0.01 μM prazosin (PZ) completely blocked the effects of NE + P, returning APD50 and APD90 to 163 ± 7 and 250 ± 9 ms (not different from baseline). After incubation of isolated Purkinje fibers with pertussis toxin (1 μg/ml), which reduced the availability of a 41-kDa membrane protein for ADP ribosylation by 70 ± 7% (n = 4, P < 0.05), YO failed to reverse the prolongation in action potential durations brought on by NE + P, but the effects of PZ were intact. The effects of α2-stimulation on β-adrenergic-induced delayed afterdepolarizations (DADs) were studied by burst pacing of Purkinje fibers in Tyrode solution containing 7.5 mM Ca2+. The DADs induced in the presence of NE + PZ (B- + α2-stimulation) were significantly smaller in amplitude and required a shorter pacing cycle length to reach threshold than those induced in the presence of NE + PZ + YO (unopposed β-adrenergic stimulation). Furthermore sustained triggered activity, seen in five of eight preparations under β-stimulation, could no longer be elicited in the presence of β- + α2-stimulation. These results suggest that the postjunctional α2-adrenergic receptors in canine Purkinje fibers are coupled to a pertussis toxin-sensitive G protein and that stimulation of these receptors leads to action potential prolongation and suppression of DADs induced by β-adrenergic stimulation.

AB - The effects of α2-adrenergic stimulation on action potentials were measured in isolated canine Purkinje fibers. Action potential durations at 50 and 90% of repolarization (APD50 and APD90) were significantly prolonged by 0.25 μM l-norepinephrine + 0.5 μM dl-propranolol (NE + P) from baseline values of 165 ± 7 and 249 ± 9 (SE) ms (n = 7) to 174 ± 7 and 265 ± 9 ms, respectively (P < 0.05 for both). Selective α2-blockade with 0.01 μM yohimbine (YO) reduced this prolongation by NE + P in APD50 and APD90 to 169 ± 7 and 256 ± 8 ms, respectively (P < 0.05 compared with NE + P). Additional selective α1-blockade with 0.01 μM prazosin (PZ) completely blocked the effects of NE + P, returning APD50 and APD90 to 163 ± 7 and 250 ± 9 ms (not different from baseline). After incubation of isolated Purkinje fibers with pertussis toxin (1 μg/ml), which reduced the availability of a 41-kDa membrane protein for ADP ribosylation by 70 ± 7% (n = 4, P < 0.05), YO failed to reverse the prolongation in action potential durations brought on by NE + P, but the effects of PZ were intact. The effects of α2-stimulation on β-adrenergic-induced delayed afterdepolarizations (DADs) were studied by burst pacing of Purkinje fibers in Tyrode solution containing 7.5 mM Ca2+. The DADs induced in the presence of NE + PZ (B- + α2-stimulation) were significantly smaller in amplitude and required a shorter pacing cycle length to reach threshold than those induced in the presence of NE + PZ + YO (unopposed β-adrenergic stimulation). Furthermore sustained triggered activity, seen in five of eight preparations under β-stimulation, could no longer be elicited in the presence of β- + α2-stimulation. These results suggest that the postjunctional α2-adrenergic receptors in canine Purkinje fibers are coupled to a pertussis toxin-sensitive G protein and that stimulation of these receptors leads to action potential prolongation and suppression of DADs induced by β-adrenergic stimulation.

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