CA2+ CALMODULIN-DEPENDENT REGULATION OF THE DENSITY OF NA+ CHANNELS IN EMBRYONIC CHICK SKELETAL-MUSCLE CELLS DURING THEIR DEVELOPMENT IN CULTURE/

Regulation of the density of voltage-dependent Na+ channels (VDNC) was studied in chick myotubes during their development in culture. The de nsity of VDNC was assessed quantitatively in terms of the maximum rate of rise (M.R.R.) of Na+ spikes. Chronic treatment of myotubes, whose density of VDNC had reached a plateau level after 6 days in culture, w ith the calmodulin (CaM) inhibitor W-7 caused a further increase in th e density. A derivative of W-7. known as W-5, which has a lower affini ty for CaM than does W-7, was without effect. A selective inhibitor of Ca2+/CaM-dependent protein kinase II (CaM-KII), namely, KN-62, also c aused an increase in the density of VDNC when its effect was examined in mature myotubes. A structural analogue of KN-62, namely, KN-04, whi ch is a much less effective inhibitor of CaM-KII, was without effect. These results suggest that density of VDNC in developing myotubes is r egulated by Ca2+/CaM and CaM-KII. However. the role of CaM-KII in this regulation is not straightforward since it appears to decrease the de nsity of VDNC in mature myotubes, but to increase their density in imm ature myotubes. (C) 1994 Academic Press, Inc.