Demonstration of calcium-activated transient outward chloride current and delayed rectifier potassium currents in Swine atrial myocytes.
Cellular electrophysiology is not fully understood in the atrium of pig heart. The objective of the present study was to determine whether transient outward current (I(to)), ultra-rapid delayed rectifier potassium current (I(Kur)), and rapid and slow delayed rectifier K(+) currents (I(Kr) and I(Ks)) were present in pig atrium. The whole-cell patch technique was applied to record membrane currents and action potentials in myocytes isolated from pig atrium. It was found that an I(to) was activated upon depolarization voltage steps to between -10 and +60 mV from -50 mV in pig atrial cells, and the I(to) was sensitive to the inhibition by the blockade of L-type calcium (Ca(2+)) current, showed a "bell-shaped" I-V relationship, typical of I(to2) (i.e. I(Cl.Ca)). The I(to2) was inhibited by the chloride (Cl(-)) channel blocker anthracene-9-carboxylic acid (9-AC, 200 micromol/l) or 4,4'-diisothiocyanostilben-2,2'disulfonic acid (200 micromol/l), and by Cl(-) substitution in the superfusate. I(Kur) was found in pig atrial myocytes, and the current showed properties of weak inward rectification and use- and frequency-dependent reduction. I(Kur) was resistant to tetraethylammonium, but sensitive to inhibition by 4-aminopyridine (4-AP) (IC(50) = 71.7 +/- 3.5 micromol/l). In addition, E-4031-sensitive I(Kr) and chromanol 293B-sensitive I(Ks) were observed in pig atrial myocytes. Blockade of I(to2), I(Kur), I(Kr) or I(Ks) with corresponding blockers significantly prolonged atrial action potentials. These results indicate that Ca(2+)-activated I(to2), 4-AP-sensitive I(Kur), E-4031-sensitive I(Kr), and 293B-sensitive I(Ks) are present in pig atrial myocytes, and these currents play important roles in action potential repolarization of pig atria.
Li
Gui-Rong
GR
Department of Medicine Institute of Cardiovascular Science and Medicine, L8-01, Laboratory Block, Faculty of Medicine Building, The University of Hong Kong, 21 Sassoon Road, Pokfulam, Hong Kong, SAR, China. grli@hkucc.hku.hk
Sun
Haiying
H
To
Jensen
J
Tse
Hung-Fat
HF
Lau
Chu-Pak
CP
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D018118:Chloride Channels / Q000737:chemistry*; D004594:Electrophysiology; D006325:Heart Atria / Q000166:cytology / Q000473:pathology*; D020128:Inhibitory Concentration 50; D008564:Membrane Potentials; D009206:Myocardium / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000737:chemistry / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000737:chemistry; D012433:Ryanodine / Q000494:pharmacology; D013552:Swine; D019789:Tetraethylammonium / Q000494:pharmacology; D013997:Time Factors
D000873:Anthracenes; D018118:Chloride Channels; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D012433:Ryanodine; D019789:Tetraethylammonium; C010030:9-anthroic acid; D015761:4-Aminopyridine; D011188:Potassium; D002118:Calcium