蜘蛛毒によるMechanosensitive BK チャネルの阻害

Mechanosensitive channels (MSCs) have been suggested to play crucial roles in cell physiology, however, never clarified yet. One of the reasons is the lack of specific blockers to MSCs. To date gadolinium and aminoglycosides have been used as potent but nonspecific blockers to the MSCs. Very recently, the peptide GsMTx-4 from spider (Grammostola spatulata) venom was reported to be a promising candidate for a specific blocker of MSCs. However, its actions on MSCs are poorly characterized. Here we report that GsMTx-4 can block the stretch activated and Ca²⁺-activated big K channel (SAKcaC) from chick embryonic myocardial cells. Single channel currents of the SAKcaC were recorded mostly from excised inside-out patches and negative pressure was applied in the pipette to stretch the patch. Open probability of the channel (Po) was significantly reduced by the μM range of GsTMx-4 without changing its single channel conductance, suggesting that the peptide blocks the channel in a slow blockade manner. Whether GsTMx-4 modifies the mechano-gating of SAKcaC or not is under investigation. GsTMx-4 also blocked the SAKcaC, which was cloned and expressed in CHO cells, in a similar manner. However, GsTMx-4 slightly inhibited the mutated SAKcaC that lacks mechanosensitivity but preserved original voltage and Ca²⁺dependencies of the SAKcaC. Although we do not know this mechanism yet, the last result provides a possibility that GsTMx-4 would work as a blocker specific to MSCs. [Jpn J Physiol 54 Suppl:S128 (2004)]