Hyaluronan activates calcium-dependent chloride currents in Xenopus oocytes

Hyaluronan (5 mg/ml) activated an oscillatory inward current of up to 200 nA in oocytes held voltage-clamped at -60 mV. The reversal potential of the current was -25 +/- 1 mV (n = 5), close to the Cl- equilibrium potential for oocytes. The response was dose-dependent over the concentration range 0.2-10 mg/ml, independent of external Ca2+, but abolished by injection of EGTA, a Ca2+ chelator. In addition, hyaluronan sensitivity in oocytes was seasonal with 91% of the responses occurring between June and December. Pre-heating hyaluronan to > 50 degrees C reduced the response; at 70-85 degrees C the response was lost. Cooling the heated hyaluronan, however, restored the activity. Hyaluronan which had been previously digested with 10 mg/ml hyaluronidase for 1-7 h (at 37 degrees C) activated smaller currents: for digestions > 7 h the current-activating ability of hyaluronan was abolished. The results are discussed in relation to possible signal transduction pathways involving hyaluronan.