Ultrasound-induced cell membrane porosity

Recent studies of ultrasound (US) methods for targeted drug delivery and nonviral gene transfection revealed new, advantageous possibilities. These studies utilized US contrast agents, commonly stabilized micro-bubbles, to facilitate delivery and suggested that US delivery resulted from cell sonoporation, the formation of temporary pores in the cell membrane induced by US. Using voltage clamp techniques, we obtained real-time measurements of sonoporation of single Xenopus oocyte in the presence of Optison(TM), an agent consisting of albumin-shelled C,F, gas bubbles (mean diameter 3.2 mum). Ultrasound increased the transmembrane current as a direct result of decreased membrane resistance due to pore formation. We observed a distinct delay of sonoporation following US activation and characteristic stepwise increases of transmembrane current throughout US duration. We discovered that the resealing of cell membrane following US exposure required Ca2+ entering the cell through US-induced pores. (E-mail: cxd54@cwru.edu) (C) 2004 World Federation for Ultrasound in Medicine Biology.