Influence of the whole-cell patch-clamp configuration on electrophysiological properties of the voltage-dependent sodium current expressed in MDA-MB-231 breast cancer cells.
Voltage-gated ionic channels are known to be involved in oncogenesis. However, only a few studies describe the functional characteristics of these channels or the mechanisms by which they are involved in the proliferation and invasive processes. Breast cancer cells proliferate and migrate under the constant activation of growth factors, hormones, extracellular matrix interactions, etc. It would thus not be surprising if the activity of the ionic channels was modulated by intracellular regulation pathways such as kinases or phosphatases, which in turn can affect oncogenic properties. In the present study, we investigated some of the electrophysiological properties of the fast inward sodium current found in the breast cancer cell line MDA-MB-231 with two configurations of the patch-clamp technique. With perforated patch, a configuration which allows to keep the cytoplam intact, the mean current amplitude was lower, the relative conductance-voltage relationship was shifted to more positive potentials and the recovery from inactivation was accelerated when compared to ruptured patch, where the cytoplasm is dialysed by the intrapipette solution. There was no difference in availability-voltage (pseudo-steady-state inactivation) relationship and in time to peak of the current. These results suggest that regulation mechanisms, possibly involving kinases or phosphatases, are switched off when the cytoplasm is diluted. We propose that such a regulation can modulate the functioning of the channels even in the absence of membrane voltage changes, which in turn can affect oncogenic properties. This finding is of importance when evaluating the physiopathological role of ionic channel in cancer development.
Nutrition, Croissance et Cancer, Emi-U 0211 Inserm, Faculté de Médecine, 2 Bd Tonnellé, 37032 Tours, France.
Sébastien
S
Roger
Pierre
P
Besson
Jean-Yves
JY
Le Guennec
D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D004594:Electrophysiology; D015640:Ion Channel Gating / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D018408:Patch-Clamp Techniques; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010770:Phosphotransferases / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000502:physiology*
D015222:Sodium Channels; D012964:Sodium; D010770:Phosphotransferases; D010744:Phosphoric Monoester Hydrolases