hKv4.3 channel characterization and regulation by calcium channel antagonists.
Relative expression pattern of short and long isoforms of hKv4.3 channels was evaluated by RT-PCR and RPA. Electrophysiological studies were performed in HEK293 cells transfected with short or long hKv4.3 cDNA. The long variant L-hKv4.3 was the only form present in lung, pancreas, and small intestine. The short variant S-hKv4.3 was predominant in brain whereas expression levels of the two isoforms were similar in cardiac and skeletal muscles. Properties of the ionic channels encoded by L-hKv4.3 and S-hKv4.3 cDNAs were essentially similar. Cadmium chloride and verapamil inhibited hKv4.3 current (with EC50s of 0.110 +/- 0.004 mM and 492.9 +/- 15.1 microM, respectively). Verapamil also accelerated current inactivation. Another calcium channel antagonist nicardipine was found inactive. In conclusion, this study confirms that both isoforms underlie the transient outward potassium current. Moreover, calcium channel inhibitors markedly affect hKv4.3 current, an effect which must be considered when evaluating transient outward potassium channel properties in native tissues.
Calmels
T P
TP
Department of Cardiovascular Pharmacology, SmithKline Beecham Laboratories Pharmaceutiques, 4 Rue du Chesnay Beauregard, 35760 Saint-Grégoire, France.
Faivre
J F
JF
Cheval
B
B
Javré
J L
JL
Rouanet
S
S
Bril
A
A
D019256:Cadmium Chloride / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D015221:Potassium Channels / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D020033:Protein Isoforms / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051672:Shal Potassium Channels; D013997:Time Factors; D014018:Tissue Distribution; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; C497021:KCND3 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D020033:Protein Isoforms; D012333:RNA, Messenger; D051672:Shal Potassium Channels; D014700:Verapamil; D019256:Cadmium Chloride