VOLTAGE-DEPENDENT L-TYPE CA CHANNELS AND A NOVEL TYPE OF NONSELECTIVECATION CHANNEL ACTIVATED BY CAMP-DEPENDENT PHOSPHORYLATION IN MESODERM-LIKE (MES-1) CELLS

Undifferentiated P19 embryonal carcinoma cells (ECC P19), the P19-deri ved clonal cell lines END-2 (visceral endoderm-like), EPI-7 (epithelio id ectoderm-like), MES-1 (mesoderm-like) and a parietal yolk sac cell line (PYS-2) were used as cellular models to examine the functional ex pression of voltage-dependent Ca channels and other Ca-permeable catio n channels at various stages of early embryonic development. Whole-cel l currents were recorded by means of the patch clamp technique. Wherea s more than 75% of MES-1 cells possessed Ca channel currents, neither P19, END-2, EPI-7 nor PYS-2 cells had detectable voltage-dependent inw ard currents. Ca channel currents of MES-1 cells were highly sensitive towards 1,4-dihydropyridines and blocked by cadmium. Adrenaline (10 m uM) caused Ca channel stimulation in only 14% of MES-1 cells examined. However, in 62% of the cells adrenaline activated a linear current co mponent which under physiological conditions reversed close to 0 mV. R emoval of extracellular Na+ suppressed the adrenaline-induced inward c urrent, while reducing extracellular Cl- had no significant effect. Th ese findings suggest that the adrenaline-induced current is carried th rough non-selective cation channels which were found to be permeable f or Na+, K+, Cs+ >> Ca2+. Remarkably, the intracellular signalling path way for activation of the non-selective cation current involved the ca scade of reactions leading to cAMP-dependent phosphorylation, a regula tory pathway well known for cardiac Ca channels. A possible functional role of adrenaline-induced nonselective cation currents and Ca channe ls in embryonal development is discussed.