TY - JOUR
T1 - Electrophysiological effects of α2-adrenergic stimulation in canine cardiac Purkinje fibers
AU - Samson, R. A.
AU - Cai, J. J.
AU - Shibata, E. F.
AU - Martins, J. B.
AU - Lee, H. C.
PY - 1995
Y1 - 1995
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.
KW - G protein
KW - UK-14304
KW - action potential duration
KW - delayed afterdepolarization
KW - α-adrenergic receptor
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U2 - 10.1152/ajpheart.1995.268.5.h2024
DO - 10.1152/ajpheart.1995.268.5.h2024
M3 - Article
C2 - 7771552
AN - SCOPUS:0029032131
SN - 0363-6135
VL - 268
SP - H2024-H2035
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 5 37-5
ER -