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Saxitoxin blocks L-type/Ca
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DOI：10.1124/jpet.103.056564.png)
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摘要
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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,I-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,I-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 muM; Calbiochem) and TTX (60 muM; Sigma-Aldrich) completely blocked I-Na in mouse VMs. However, STX at 10 muM also reduced I-Ca,I-L in mouse VM by 39% (P<0.0001; n=14), whereas TTX at 60 μM had no effect on I-Ca,I-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 muM; Sigma-Aldrich) only reduced the amplitude of the [Ca2+](i) transients by 9% (P=0.003; n=5). STX (10 muM) obtained from Sigma-Aldrich showed a similar inhibitory effect on I-Ca,I-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.
Keyword:
MOUSE VENTRICULAR MYOCYTES
SODIUM-CHANNEL
NA+-CA2+ EXCHANGER
CALCIUM CURRENTS
NA+ CHANNEL
TETRODOTOXIN
CA2+
HEART
CONTRACTION
TRANSIENTS
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期刊
IF:
3.8
论文数:
1.0W
被引数:
2.0W
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