Effects of Palytoxin on Guinea Pig Tracheal Strips

The effects of palytoxin (PTX) on airway smooth muscle were investigated in opened rings of guinea pig trachea. Concentrations of PTX from 10 pM to 100 nM caused contractions of tracheal strips, with maximal contractions approximately 80% of those in response to 120 mM potassium. Tension increased to its maximum in approximately 5 min with 100 nM PTX, then decreased to or near resting tension over the next 60 min. Contractions were larger when the epithelium was removed. Exposure to high (100 nM) concentrations of PTX markedly reduced subsequent contractions to PTX but had less effect on potassium-induced contractions. In zero-calcium solution the rate of contraction was slowed but the maximal contraction was not reduced. The addition of a calcium channel blocker (verapamil) markedly reduced the contractions and a calcium chelator (EGTA) abolished them. Contractions to PTX in zero-calcium media suggested that tracheal cartilage was serving as a calcium source, as it has been previously reported to do. Potassium removal and sodium reduction also greatly reduced contractions. These data are consistent with other observations suggesting that PTX may form pores through which sodium leaks into the cell. PTX was also found to differ from ouabain in its mode of action.