Sustained depolarization-induced outward current in human atrial myocytes. Evidence for a novel delayed rectifier K+ current similar to Kv1.5 cloned channel currents.

摘要: Depolarization of human atrial myocytes activates a transient outward current that rapidly inactivates, leaving sustained after continued depolarization. To evaluate the ionic mechanism underlying this (Isus), we applied whole-cell voltage-clamp techniques to single isolated from right specimens obtained patients undergoing coronary bypass surgery. The magnitude Isus was constant for up 10 seconds at +30 mV and unaffected by 40 mmol/L tetraethylammonium, 100 nmol/L dendrotoxin, 1 Ba2+, 0.1 mumol/L atropine, or removal Cl- in superfusate. could be distinguished 4-aminopyridine (4AP)-sensitive (Ito1) differences voltage-dependent inactivation (1000-millisecond prepulse -20 reduced Ito1 91.7 +/- 0.1% [mean SEM], P < .001, versus 9.4 0.4% reduction Isus) 4AP sensitivity (IC50 block Ito1, 1.96 mmol/L; Isus, 49 mumol/L). activation had voltage threshold near -30 mV, half-activation -4.3 slope factor 8.0 mV. not inactivated 1000-millisecond prepulses but 16 8% (P .05) holding potential relative values -80 activated very rapidly, with time constants (tau) 25 degrees C ranging 18.2 1.8 2.1 0.2 milliseconds -10 +50 two orders faster than previously described kinetics rapid component delayed rectifier K+ current. At C, greatly slowed (tau +10 46.7 4.1 milliseconds; tau 7.1 0.8 .01), envelope tails test satisfied. reversal tail currents changed linearly log [K+]o (slope, 55.3 2.9 per decade), fully current-voltage relation showed substantial rectification. Selective inhibition 50 increased action duration 66 11% .01). In conclusion, is due activating current, which shows limited slow inactivation, insensitive highly sensitive 4AP. These properties resemble characteristics channels encoded Kv1.5 group cardiac cDNAs may represent physiologically significant manifestation such atrium.