Expression of voltage-gated K+ channels in human atrium.
Voltage-gated K(+) channels underlie repolarisation of the cardiac action potential and represent a potential therapeutic target in the treatment of cardiac dysrhythmias. However, very little is known about the relative expression of K(+) channel subunits in the human myocardium. We used a semi-quantitative RT-PCR technique to examine the relative expression of mRNAs for the voltage-gated K(+) channel subunits, Kv1.2, Kv1.4, Kv1.5, Kv2.1, Kv4.2, Kv4.3, KvLQT1, HERG and IsK in samples of human atrial appendage. Data were expressed as a percentage expression density relative to an 18S ribosomal RNA internal standard. The most abundant K(+) channel mRNAs were Kv4.3 (80.7 +/- 10.1 %), Kv1.5 (69.7 +/- 11.2 %) and HERG (55.9 +/- 21.5 %). Significant expression of KvLQT1 (33.5 +/- 5.5 %,) and Kv1.4 (26.7 +/- 9.6 %) was also detected. Levels of mRNAs for Kv1.2 and IsK were very low and neither Kv2.1 nor Kv4.2 mRNA were detected in any experiments. Whole-cell patch-clamp techniques were used to examine the outward currents of isolated human atrial myocytes at 37 degrees C. These recordings demonstrated the existence of transient (I(to1)) and sustained (I(so)) outward currents in isolated human atrial myocytes. I(to1), and not I(so), showed voltage-dependent inactivation during 100 ms pre-pulses. Both I(to1) and I(so) were inhibited by high concentrations (2 mM) of the K(+) channel blocker, 4-aminopyridine (4-AP). However, lower concentrations of 4-AP (10 microM) inhibited I(so) selectively. I(to1) recovered from inactivation relatively rapidly (tao approximately 21 ms). These data, with published information regarding the properties of expressed K(+) channels, suggest that Kv4.3 represents the predominant K(+) channel subunit underlying I(to1) with little contribution of Kv1.4. The sensitivity of Iso to very low concentrations of 4-aminopyridine and the relatively low expression of mRNA for Kv1.2 and Kv2.1 is consistent with the major contribution of Kv1.5 to this current. The physiological significance of the expression of KvLQT1 and Kv1.4 mRNA in the human atrium warrants further investigation.
Bertaso
Federica
F
Cell Signalling Group, Department of Renal Medicine, Guy's, King's & St Thomas' School of Medicine, King's College London, Bessemer Road, London, SE5 7PJ, United Kingdom.
Sharpe
Claire C
CC
Hendry
Bruce M
BM
James
Andrew F
AF
D015761:4-Aminopyridine / Q000494:pharmacology; D004553:Electric Conductivity; D005260:Female; D006325:Heart Atria; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000502:physiology; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051672:Shal Potassium Channels
C497018:KCND2 protein, human; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D020033:Protein Isoforms; D012333:RNA, Messenger; D051672:Shal Potassium Channels; D015761:4-Aminopyridine