Electrophysiological characterization of voltage-gated Na+ current expressed in the highly metastatic Mat-LyLu cell line of rat prostate cancer
✍ Scribed by Julia A. Grimes; Mustafa B. A. Djamgoz
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 245 KB
- Volume
- 175
- Category
- Article
- ISSN
- 0021-9541
No coin nor oath required. For personal study only.
✦ Synopsis
Voltage-gated Na / channels, classically associated with impulse conduction in excitable tissues, are also found in a variety of epithelial cell types where their possible functions are not known so well. We have previously reported expression of a voltage-gated Na / channel specifically in the highly metastatic Mat-LyLu rat prostate cancer cell line; blockage of the current with tetrodotoxin (TTX) significantly reduced the invasiveness of the cells in vitro, suggesting that the channel may have a functional role in metastasis. The aim of the present study was to characterize this current using the whole-cell patch clamp recording technique, and compare it to Na / currents found in various other tissues. The inward current of the Mat-LyLu cells was abolished completely, but reversibly, in Na / -free solution, confirming that Na / was indeed the permeant ion. Activation occurred at 040 mV and currents reached a maximal amplitude at around 6 mV. Boltzmann fits to current activation and steady-state inactivation revealed that the currents were half activated at about 015 mV and half inactivated at 080 mV. Both current inactivation and recovery from inactivation followed a double-exponential time course with fast and slow components. The Na / currents were highly sensitive to block by TTX (IC 50 à 18 nM), whilst 1 mM m-conotoxin GIIIA mostly had no effect. 100 mM Cd 2/ also had no effect on the current, whilst 2.5 mM Cd 2/ , Mn 2/ , and Co 2/ each caused a depolarizing shift in activation and a reduction in peak conductance of around 20%. In conclusion, the Na / channel expressed in the highly metastatic Mat-LyLu cell line appeared to have electrophysiological and pharmacological properties of TTX-sensitive channels. Further work is needed, however, to elucidate the exact nature of the channel protein and the mechanism(s) of its involvement in cellular invasiveness.