FIG 8.

Micafungin evokes a prolonged rise in the PTV partly dependent on extracellular Ca²⁺. (A) In Ca²⁺-containing solution, micafungin induced a prolonged rise in the PTV, up to 165% of the basal PTV. The PTV slowly declined under long-term micafungin exposure. (B) The micafungin-induced rise in the PTV was partly dependent on the extracellular Ca²⁺ concentration, since the observed rise in the PTV was reduced in Ca²⁺-free buffer solution. Still, under prolonged micafungin exposure, the PTV declined. (C) The inhibition of PKA using H-89 reduced the basal PTV, while subsequent application of micafungin induced a significant rise in the PTV, which declined after reaching a maximum velocity. (D) Micafungin induced a significant rise in the PTV either in Ca²⁺-containing or Ca²⁺-free medium. However, the PTV in Ca²⁺-free buffer solution was significantly lower than that in Ca²⁺-containing buffer solution. In tracheae treated with BAPTA-AM to reduce [Ca²⁺]_i, micafungin induced a significant transient rise in the PTV. H-89, the inhibitor of the PKA signal transduction pathway, did not prevent the micafungin-induced rise in the PTV. The depletion of mitochondrial Ca²⁺ stores and simultaneous interruption of mitochondrial ATP synthesis using DNP did not prevent the micafungin-evoked rise in the PTV (horizontal bars in experimental recordings present exposure periods of defined pharmacological agents; n, number of individual experiments; time scale bars are present in all individual panels; *, P < 0.05; **, P < 0.01; ***, P < 0.001; Mann-Whitney U test).