tetrodotoxin sensitivity of the vertebrate cardiac na+ current河豚毒素敏感的脊椎动物心脏na +电流.pdf

Mar. Drugs 2011, 9, 2409-2422; doi:10.3390/md9112409 OPEN ACCESS Marine Drugs ISSN 1660-3397 /journal/marinedrugs Article Tetrodotoxin Sensitivity of the Vertebrate Cardiac Na+ Current Matti Vornanen *, Minna Hassinen and Jaakko Haverinen Department of Biology, University of Eastern Finland, Joensuu 80101, Finland; E-Mails: minna.hassinen@uef.fi (M.H.); jaakko.haverinen@uef.fi (J.H.) * Author to whom correspondence should be addressed; E-Mail: matti.vornanen@uef.fi; Tel.: +358-13-2513-383; Fax: +358-13-2513-590. Received: 20 September 2011; in revised form: 2 November 2011 / Accepted: 10 November 2011 / Published: 21 November 2011 Abstract: Evolutionary origin and physiological significance of the tetrodotoxin (TTX) resistance of the vertebrate cardiac Na+ current (INa) is still unresolved. To this end, TTX sensitivity of the cardiac INa was examined in cardiac myocytes of a cyclostome (lamprey), three teleost fishes (crucian carp, burbot and rainbow trout), a clawed frog, a snake (viper) and a bird (quail). In lamprey, teleost fishes, frog and bird the cardiac INa was highly TTX-sensitive with EC50-values between 1.4 and 6.6 nmol·L− 1. In the snake heart, about 80% of the I was TTX-resistant with EC value of 0.65 μmol·L− 1, the rest being Na 50 TTX-sensitive (EC50 = 0.5 nmol·L− 1). Although TTX-resistance of the cardiac INa appears to be limited to mammal