BLOCK OF CALCIUM-ACTIVATED POTASSIUM CHANNELS IN MAMMALIAN ARTERIAL MYOCYTES BY TETRAETHYLAMMONIUM IONS

The effects of tetraethylammonium ions (TEA+) and tetrapentylammonium ions (TPeA+) on Ca2+-activated K+ (K(Ca)) channels were studied in membrane patches from mesenteric arterial myocytes. External TEA+ produced a flickery block. The concentration dependence for reduction in mean unitary current was consistent with 1:1 binding, with dissociation constants (K(d)) in rat and rabbit of 196 and 159-mu-M at 0 mV, and the block was weakly voltage dependent. Rate constants for blocking and unblocking were 380 mM-1 .ms-1 and 73 ms-1, respectively. In patches containing several channels TEA+ reduced average current to the same extent as mean unitary current, implying that TEA+ block is independent of the channel state. Block was unaffected by raising external K+ to 120 mM. External TPeA+ blocked with slower kinetics and lower affinity than TEA+ (K(d), 1.49 mM). The sulfonylurea glibenclamide (10-100-mu-M), the hyperpolarizing vasodilator cromakalim (5 mu-M), and internal ATP (1 mM) were without effect on channel activity. We conclude that TEA+ is a relatively effective blocker of single K(Ca) channels of arterial smooth muscle and should block macroscopic currents equally well, whereas external TPeA+ is about eight times less effective.