J. Arreola et al., NA-LINE( CHANNELS IN CARDIAC AND NEURONAL CELLS DERIVED FROM A MOUSE EMBRYONAL CARCINOMA CELL), Journal of physiology, 472, 1993, pp. 289-303
1. Cells from a pluripotent murine embryonal carcinoma cell line (P19)
were differentiated in vitro into cells with neurone- and cardiac-lik
e phenotypes. Cells treated with 0.5 mum retinoic acid developed into
neurone-like cells possessing extensive neurites. Dimethyl sulphoxide
treatment (0.5%) produced large, spontaneously contracting cell aggreg
ates with many properties of cardiac cells. 2. The neurone- and cardia
c-like cells contained voltage-sensitive Na+ channels with properties
similar to those of native neuronal and cardiac cells. 3. We used whol
e-cell patch clamp techniques to measure inward currents from the neur
one- and cardiac-like cells. Undifferentiated (untreated) cells had on
ly small inward currents (peak of -0.15 nA in 150 mm external Na+). Th
e peak inward current in the neurone-like and cardiac-like cells was -
1.2 nA (in 154 mm external Na+) and -2.8 nA (in only 46 mm Na+), respe
ctively. These large currents were absent when the external solution c
ontained no Na+. 4. Tetrodotoxin (TTX) blocked the Na+ currents in the
neurone-and cardiac-like cells in a dose-dependent manner. The K(d) f
or TTX block of the Na+ current in the neurone-like cells was 6.7 nm.
The Na+ current in the cardiac-like cells was much more resistant to T
TX; the half-blocking concentration was two orders of magnitude higher
, 710 nm. 5. The kinetic properties of the Na+ channel currents in the
neurone- and cardiac-like cells were similar but developed over somew
hat different voltage ranges. The voltage sensitivity of activation wa
s similar in both cell t pes but the activation midpoint voltage was d
ifferent: -12 mV in the neuronal cells and -34 mV for cardiac cells. I
nactivation of the neuronal Na+ channels had a mid-point near -47 mV a
nd was more sensitive to the membrane voltage than inactivation of the
cardiac channels. The mid-point of inactivation for the cardiac Na+ c
hannels was -80 mV.