The role of voltage-gated Na+ channels in excitation-contraction coupling of rat heart determined by BmK I, an alpha-like scorpion neurotoxin.
A mechanism underlying the increase in rat heart contractility modulated by BmK I, an alpha-like scorpion neurotoxin, was investigated using whole-cell patch-clamp and fluorescence digital imaging techniques. Results showed that (a) L-type Ca2+ current could not be modified by 500 nM BmK I; (b) The inactivation process of Na+ current was significantly delayed with no change of its amplitude; (c) The overall intracellular Na+ and Ca2+ concentration could be augmented in the presence of BmK I; (p<0.05); (d) The increase of free intracellular Ca2+ concentration induced by BmK I was inhibited completely by 5 mM NiCl2 (p<0.05), an inhibitor of Na+-Ca2+ exchanger; (e) The spontaneous Ca2+ release induced by 10 mM caffeine from sarcoplasmic reticulum could not be modulated by 500 nM BmK I in the absence of external Ca2+. These results indicate that cardiac voltage-gated Na+ channels are also targets of BmK I. Na+ accumulation through Na+ channels can trigger sarcoplasmic reticulum Ca2+ release in rat cardiac myocytes via reverse-mode Na+-Ca2+ exchanger. Furthermore, Ca2+ release from sarcoplasmic reticulum induced by BmK I most likely involves a Ca2+-induced release mechanism.
Sun
Hai-Ying
HY
The Key Laboratory of Neurobiology, Institute of Physiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue-Yang Road, Shanghai 200031, PR China.
Zhou
Zhao-Nian
ZN
Ji
Yong-Hua
YH
D000818:Animals; D002118:Calcium / Q000378:metabolism; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D009532:Nickel / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D012604:Scorpion Venoms / Q000633:toxicity*; D015222:Sodium Channels / Q000187:drug effects* / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D012604:Scorpion Venoms; D015222:Sodium Channels; D019831:Sodium-Calcium Exchanger; C105338:makatoxin I; C022838:nickel chloride; D009532:Nickel; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium