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+ (KCa) 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 (Kd) in rat and rabbit of 196 and 159 microM 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+ (Kd, 1.49 mM). The sulfonylurea glibenclamide (10-100 microM), the hyperpolarizing vasodilator cromakalim (5 microM), and internal ATP (1 mM) were without effect on channel activity. We conclude that TEA+ is a relatively effective blocker of single KCa channels of arterial smooth muscle and should block macroscopic currents equally well, whereas external TPeA+ is about eight times less effective.
Langton
P D
PD
Department of Physiology, University of Leicester, United Kingdom.
Nelson
M T
MT
Huang
Y
Y
Standen
N B
NB
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001158:Arteries / Q000166:cytology / Q000378:metabolism*; D001578:Benzopyrans / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D019806:Cromakalim; D004594:Electrophysiology; D005905:Glyburide / Q000494:pharmacology; D007477:Ions; D007700:Kinetics; D011188:Potassium / Q000037:antagonists & inhibitors*; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D011758:Pyrroles / Q000494:pharmacology; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology*
D001578:Benzopyrans; D007477:Ions; D015221:Potassium Channels; D011758:Pyrroles; D000644:Quaternary Ammonium Compounds; D013757:Tetraethylammonium Compounds; D019806:Cromakalim; D019789:Tetraethylammonium; D000255:Adenosine Triphosphate; C027435:tetrapentylammonium; D011188:Potassium; D005905:Glyburide; D002118:Calcium