ISSN:
1432-1017
Keywords:
Single cardiac K+ channels
;
Gating
;
Quinidine
;
Verapamil
;
Channel-associated binding site
;
Heart muscle
Source:
Springer Online Journal Archives 1860-2000
Topics:
Biology
,
Physics
Notes:
Abstract Elementary K+ currents through cardiac outwardly rectifying K+ channels were recorded in insideout patches excised from cultured neonatal rat cardiocytes at 19 °C and at 9 °C. By studying the inhibitory effects of tetraethylammonium (TEA), quinidine and verapamil, the properties of this novel type of K+ channel were further characterized. Internal TEA (50 mmol/1) evoked a reversible decline of iunit to 62.7 + 2.7% of control (at −7 mV), without significant changes of open state kinetics, indicating a blockade of the open K+ pore with kinetics too fast to be resolvable at 1 kHz. This TEA blockade was e-fold voltage-dependent, with a decrease of the apparent KD( TEA) from 102 mmol/1 at −37 mV to 65 mmol/1 at +33 mV and, furthermore, became accentuated on lowering the internal K+ concentration. Thus, TEA competes with the permeant K+ for a site located in some distance from the cytoplasmic margin, within the K+ pore. Quinidine (100 μmol/l), like verapamil (40 μmol/1) reversibly depressed iunit to about 80% of the control value (at −7 mV), but drug-induced fast flicker blockade proved voltage-insensitive between −27 mV and +23 mV These drugs gain access to a portion of the pore distinct from the TEA binding site whose occupancy by drugs likewise blocks K+ permeation. Both drugs showed a greater potency to depress Po which, with quinidine,decreased reversibly to38.6 ± 11.1% (at −7 mV) and, with verapamil to 24.9 ± 9.1%(at −7 mV), mainly by an increase of the prolonged closed state (C,). This alteration of the gating process also includes a sometimes dramatic shortening of the open state. Most probably, cardiac K(outw.-rect.) +K+ outw.-rect. channels possess a second drug-sensitive site whose occupancy by quinidine or verapamil may directly or allosterically stabilize their non-conducting configuration.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00180164
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