RESTRICTED ION FLOW AT THE NUCLEAR-ENVELOPE OF CARDIAC MYOCYTES

Flow of small ions across the nuclear envelope (NE) is thought to occu r without restriction through large diameter nuclear pore complexes (N PCs). However, investigations with electron and fluorescence microscop y, and with patch-clamp and microelectrode electrophysiology, suggest that in many animal and plant cell types small ions move through a bar rier having the signature of large conductance nuclear ion channels (N ICs). As nucleocytoplasmic transport and gene activity are regulated b y cytoplasmic signals and as it has recently been shown by this invest igator that cardiac NICs are sensitive to cAMP-dependent processes (1) , it was considered relevant to further investigate the effects of var ious cytosolic signals on NIC activity. Ion species substitution demon strated that K+ is the major species responsible for NIC currents. The Na-channel blocker tetrodotoxin (TTX, 100 muM) and the Ca-channel blo cker diltiazem (100 muM) had no effect, indicating no relation of NICs to Na- or Ca-channels in transit to the cell surface membrane. Zn2+ ( 100 muM) blocked NIC activity, suggesting a dual role in nucleocytopla smic transport and gene function. GTP did not produce measurable effec t. However, its nonhydrolyzable analogue GTP-gamma-S (10 muM) suppress ed NIC activity, suggesting a role for GTP hydrolysis in NIC function. Deoxynucleotides (dNTPs, 200 muM) produced a transient increase in NI C activity, pointing to a modulation of NIC function by nucleic acid s ubstrates. These results indicate a role for NICs in mediating: (a) co ntrol of gene activity by transduction and other cytosolic signals, an d (b) nuclear demands and response to such signals.