BmK I, an alpha-like scorpion neurotoxin, specifically modulates isolated rat cardiac mechanical and electrical activity.
In this study, cardiotonic and cardiotoxic effects of Buthus martensi Karsch (BmK) I, a modulator of voltage-gated sodium channels, were investigated on the isolated rat hearts. The results showed that BmK I evoked complex effects characterized by a change in both cardiac mechanical and electrical activity. Langendorff perfusion showed that: (1) maximal left ventricular developed pressure (LVDP(max)) and dp/dt(max) were markedly increased by BmK I (0.5-10 micromol/L) in a dose-dependent manner (n=6, P<0.05), positive chronotropic effects were also induced by BmK I (n=6, P<0.05); (2) negative inotropic action and bradycardia could be elicited at a larger dose of BmK I (20 micromol/L); (3) the coronary flow varied inversely with the positive inotropic effects, coronary flow reduced during positive inotropic effects from 14.5 to 8.6 ml/min after administration of 500 nmol/L BmK I (n=6, P<0.05). In addition, tachycardia and complex cardiac arrhythmias were induced by BmK I (0.5-10 micromol/L). The modulating of BmK I on the heart mechanical, electrical activity could be partially recovered after washing. As propranolol was applied to block the release of catecholamines before administration of BmK I, suggesting that the changes in cardiac mechanical and electrical activity induced by BmK I might not due to catecholamine release from the nerve terminal and subsequent stimulation of the beta-adrenoceptor but attributable to the modulation of BmK I on cardiac voltage-gated sodium channels.
Sun
Hai-Ying
HY
Institute of Physiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031.
Zhu
Hai-Feng
HF
Ji
Yong-Hua
YH
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D004594:Electrophysiology; D066298:In Vitro Techniques; D019476:Insect Proteins; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D062554:NAV1.5 Voltage-Gated Sodium Channel; D009498:Neurotoxins / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012604:Scorpion Venoms / Q000494:pharmacology*; D026941:Sodium Channel Blockers / Q000494:pharmacology*; D015222:Sodium Channels / Q000187:drug effects
C403888:BmK M1 neurotoxin; D019476:Insect Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; D009498:Neurotoxins; C568322:Scn5a protein, rat; D012604:Scorpion Venoms; D026941:Sodium Channel Blockers; D015222:Sodium Channels