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CARDIOVASCULAR

Saxitoxin Blocks L-Type I_Ca

Cardiology Division, University of Utah Health Sciences Center, Salt Lake City, Utah (Z.S., M.S., F.L., W.H.B.); and Department of Physiology, Tokai University, Isahara, Japan (H.I.)

Saxitoxin (STX) and tetrodotoxin (TTX) are frequently used to selectively block sodium channels. In this study, we provide evidence that commercial STX also inhibits L-type Ca²⁺ currents (I_Ca,L) in adult mouse ventricular myocytes (VMs) and tsA-201 cells that were transiently cotransfected with three calcium channel subunits. We measured inhibition of sodium currents (I_Na) in mouse VMs, of I_Ca,L in mouse VM and tsA-201 cells, and intracellular calcium concentration ([Ca²⁺]_i) transients in single mouse VMs. STX or TTX was abruptly applied before the test voltage pulse using a rapid solution switcher device. STX (10 µM; Calbiochem) and TTX (60 µM; Sigma-Aldrich) completely blocked I_Na in mouse VMs. However, STX at 10 µM also reduced I_Ca,L in mouse VM by 39% (P < 0.0001; n = 14), whereas TTX at 60 µM had no effect on I_Ca,L. STX (10 µM; Calbiochem) reduced the amplitude of the [Ca²⁺]_i transients in mouse VMs by 36% (P < 0.0001; n = 10). In contrast, TTX (60 µM; Sigma-Aldrich) only reduced the amplitude of the [Ca²⁺]_i transients by 9% (P = 0.003; n = 5). STX (10 µM) obtained from Sigma-Aldrich showed a similar inhibitory effect on I_Ca,L (33%) (P < 0.0001; n = 5) in mouse VMs. STX (Calbiochem) inhibited the calcium currents of tsA-201 cells in a dose-dependent manner. This inhibition was voltage-independent. The current-voltage relationship of calcium currents in tsA-201 cells was not altered by STX. These results indicate that STX partially blocks L-type Ca²⁺ channels and thus provide further evidence that its effects are not specific for Na⁺ channels.

Address correspondence to: Dr. William H. Barry, Division of Cardiology, University of Utah Health Sciences Center, 50 North Medical Dr., Salt Lake City, UT 84132. E-mail: whbarry{at}med.utah.edu

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