Antiarrhythmogenic effects of a neurotoxin from the spider Phoneutria nigriventer.
In this study, we evaluated the effects of PhKv, a 4584 Da peptide isolated from the spider Phoneutria nigriventer venom, in the isolated rat heart and in isolated ventricular myocytes. Ventricular arrhythmias were induced by occlusion of the left anterior descending coronary artery for 15 min followed by 30 min of reperfusion. Administration of native PhKv (240 nM) 1 min before or after reperfusion markedly reduced the duration of arrhythmias. This effect was blocked by atropine, thereby indicating the participation of muscarinic receptors in the antiarrhythmogenic effect of PhKv. Notably, recombinant PhKv (240 nM) was also efficient to attenuate the arrhythmias (3.8 ± 0.9 vs. 8.0 ± 1.2 arbitrary units in control group). Furthermore, PhKv induced a significant reduction in heart rate. This bradycardia was partially blunted by atropine and potentiated by pyridostigmine. To further evaluate the participation of acetylcholine on the PhKv effects, we examined the release of this neurotransmitter from neuromuscular junctions. It was found that Phkv (200 nM) significantly increased the release of acetylcholine in this preparation. Moreover, PhKv (250 nM) did not cause any significant change in action potential or Ca(2+) transient parameters in isolated cardiomyocytes. Altogether, these findings show an important acetylcholine-mediated antiarrhythmogenic effect of the spider PhKv toxin in isolated hearts.
Department of Physiology, ICB, UFMG, Belo Horizonte, Minas Gerais, Brazil.
Alvair P
AP
Almeida
Alexandre B
AB
Andrade
Anderson J
AJ
Ferreira
Andrea C G
AC
Pires
Denis D
DD
Damasceno
Márcia N M
MN
Alves
Enéas R M
ER
Gomes
Christopher
C
Kushmerick
Ricardo F
RF
Lima
Marco Antônio M
MA
Prado
Vânia F
VF
Prado
Michael
M
Richardson
Marta N
MN
Cordeiro
Silvia
S
Guatimosim
MarcusVinícius
M
Gomez
D000109:Acetylcholine / Q000378:metabolism / Q000502:physiology; D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects; D003001:Cloning, Molecular; D004594:Electrophysiology; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects; D009469:Neuromuscular Junction / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D011729:Pyridostigmine Bromide / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013111:Spider Venoms / Q000737:chemistry*; D013112:Spiders / Q000737:chemistry*
D000889:Anti-Arrhythmia Agents; D009498:Neurotoxins; D013111:Spider Venoms; D001285:Atropine; D011729:Pyridostigmine Bromide; D000109:Acetylcholine