Suppression of slow delayed rectifier current by a truncated isoform of KvLQT1 cloned from normal human heart.
It has been suggested that the cardiac slow delayed rectifier channel is formed by the association of two subunits: IsK (also called minK) and KvLQT1. N-terminal splice variants of the human KvLQT1 gene have been identified, but the functional roles of different KvLQT1 isoforms are not clear. Using the nested 5'-rapid amplification of cDNA ends technique, we obtained a truncated isoform of KvLQT1 (termed tKvLQT1) that lacks the N-terminal cytoplasmic domain and the initial one-third of the first transmembrane domain. The function of tKvLQT1 was tested by oocyte expression, alone or together with the full-length KvLQT1 or a human IsK clone (hIsK). tKvLQT1 alone did not generate functional channels. However, it suppressed the KvLQT1 current when coexpressed with the full-length isoform. It also suppressed the slow delayed rectifier current induced by hIsK, probably by competing with the KvLQT1 subunit endogenous to Xenopus oocytes in coassembly with the hIsK subunit. On the other hand, tKvLQT1 did not suppress the expression of Kv1.4, Kv4.3, or hERG. Using the reverse transcription-polymerase chain reaction technique, we further show that the truncated and full-length isoforms are coexpressed in different regions of human heart. Therefore, tKvLQT1 may modulate the function of IKs in human cardiac myocytes.
Jiang
M
M
Department of Pharmacology, Columbia University, New York, New York 10032, USA.
Tseng-Crank
J
J
Tseng
G N
GN
D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary; D006801:Humans; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated
D018076:DNA, Complementary; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated