Cardiac dysrhythmia produced by Mesobuthus tamulus venom involves NO-dependent G-Cyclase signaling pathway
Role of G-protein coupled pathways in modulating the cardiotoxic effects produced by Indian red scorpion (Mesobuthus tamulus) venom were examined. The isometric contractions of spontaneously beating or paced (3.5 Hz) rat right atrial preparations in vitro were recorded. The cumulative concentration (0.01–3.0 μg/ml)-response of venom on spontaneously beating atria exhibited a marked decrease in rate (by 55%) and an increase in force (by 92%) only at a higher concentration (3.0 μg/ml). The venom-induced decrease in rate and increase in force were sensitive to atropine, N-ω-nitro-l-arginine methylester (NO synthase inhibitor) and methylene blue (guanylyl cyclase inhibitor). Further, nifedipine, a Ca2+ channel antagonist, blocked the force changes but not the rate changes induced by venom. In the paced atrium, on the other hand, a concentration-dependent decrease in force was observed, and at 3 μg/ml, the decrease was 50%. Pretreatment with nifedipine, but not with methylene blue, significantly attenuated the venom-induced force changes in paced atrium. The observations of this study demonstrate that the venom-induced atrial dysrhythmia is mediated through the muscarinic receptor-dependent NO-G-cyclase cell-signaling pathways.
Keywordsc-GMP Guanylyl cyclase Indian red scorpion venom l-NAME Methylene blue Nifedipine
SK wishes to thank University Grants Commission, New Delhi for the financial assistance.
- De Marco T, Dae M, Yuen-Green MS, Kumar S, Sudhir K, Keith F, Amidon TM, Rifkin C, Klinski C, Lau D, Botvinick H, Chatterjee K (1995) Iodine-123 metaiodobenzylguanidine scintigraphic assessment of the transplanted human heart: evidence for late reinnervation. J Am Coll Cardiol 25:927–931PubMedCrossRefGoogle Scholar
- Fischmeister R, Me’ry PF (1996) Regulation of cardiac calcium current by cGMP/NO route. In: Morad M, Ebashi S, Trautwein W, Kurachi Y (eds) Molecular physiology and pharmacology of cardiac ion channels and transporters. Kluwer, Dordrecht, pp 93–105Google Scholar
- Galvez A, Gimenez-Gallego G, Reuben JP, Roy-contancin L, Feigenbaum P, Kaczorowski GJ, Garcia ML (1990) Purification and characterization of a unique, potent, peptidyl probe for the high conductance calcium-activated potassium channel from venom of the scorpion Buthus tamulus. J Biol Chem 265:11083–11090PubMedGoogle Scholar
- Lindemann JP, Watanabe AM (1991) Mechanism of adrenergic and cholinergic regulation of myocardial contractility. In: Sperelakis N (ed) Physiology and pathophysiology of heart, 2nd edn. Kluwer Acad Publisher, Boston, pp 423–452Google Scholar
- Murthy KR, Vakil AE (1988) Elevation of plasma angiotensin levels in dogs by Indian red scorpion (Buthus tamulus) venom & its reversal by administration of insulin + tolazoline. Ind J Med Res 88:376–379Google Scholar
- Murthy KRK, Yeolekar ME (1986) Electrocardiographic changes in experimental myocarditis induced by scorpion (Buthus tamulus) venom. Indian Heart J 38:206–210Google Scholar
- Natu VS, Murthy KRK, Deodhar KP (2006) Efficacy of species specific anti-scorpion venom serum (AscVS) against severe, serious scorpion stings (Mesobuthus tamulus concanensis Pocock)—an experience from rural hospital in Western Maharashtra. J Assoc Physicians India 34:283–287Google Scholar
- Pandey R, Deshpande SB (2007) Aprotinin reverses ECG abnormalities induced by Mesobuthus tumulus venom in adult rats. Ind J Exp Biol 45:949–953Google Scholar
- Pedarzani P, D’hoedt D, Doorty KB, Wadsworth JD, Joseph JS, Jayasheelan K, Kini RM, Gadre SV, Sapatnekar SM, Stocker M, Strong PN (2002) Tamapin, a venom peptide from the Indian red scorpion (Mesobuthus tamulus) that targets small conductance Ca2+-activated K+ channels and after hyperpolarisation currents in central neurons. J Biol Chem 277:46101–46109PubMedCrossRefGoogle Scholar
- Strong PN, Clark GS, Armugam A, De-Allie FA, Joseph JS, Yemul V, Deshpande JM, Kamat R, Gadre SV, Gopalakrishnaakone P, Kini RM, Owen DG, Jayaseelan K (2001) Tamulus toxin: a novel potassium channel blocker from the venom of the Indian red scorpion Mesobuthus tamulus. Arch Biochem Biophys 385:138–144PubMedCrossRefGoogle Scholar
- Sun HY, Zhu HF, Ji YH (2003) BmK I, an alpha-like scorpion neurotoxin, specially modulates isolated rat cardiac mechanical and electrical activity. Acta Physiol Sin 55:530–534Google Scholar
- Teixeira CE, Bento AC, Lopes-Martins RAB, Teixeira SA, Eickestedt V, Muscara MN, Arantes EC, Giglio JR, Antunes E, Nucci G (1998) Effect of Tityus serrulatus scorpion venom on the rabbit isolated corpus cavernosum and the involvement of NANC nitrergic nerve fibres. Br J Pharmacol 123:435–442PubMedCrossRefGoogle Scholar