Heteromultimeric assembly of human potassium channels. Molecular basis of a transient outward current?

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Citation

Po S, Roberds S, Snyders DJ, Tamkun MM, Bennett PB

Heteromultimeric assembly of human potassium channels. Molecular basis of a transient outward current?

Circ Res. 1993 Jun;72(6):1326-36.

PubMed ID
8495559 [ View in PubMed
]
Abstract

To gain insight into the molecular basis of cardiac repolarization, we have expressed K+ channels cloned from ventricular myocardium in Xenopus oocytes. A recently identified human cardiac K+ channel isoform (human Kv1.4) has properties similar to the 4-aminopyridine-sensitive calcium-insensitive component of the cardiac transient outward current. However, these channels recovered from inactivation much slower than native channels. Hybrid channels consisting of subunits from different K+ channel clones (delayed rectifier channels [Kv1.1, Kv1.2, and Kv1.5] and Kv1.4) were created by coinjection of cRNAs in oocytes. Multimeric channels consisting of Kv1.4:Kv1.1, Kv1.4:Kv1.2, and Kv1.4:Kv1.5 were expressed and compared. The hybrid channels displayed characteristics of heterotetrameric channels with kinetics that more closely resembled a native cardiac transient outward current. The inactivation and recovery from inactivation of the heteromeric channels indicated that the presence of a single inactivating subunit (Kv1.4) was probably sufficient to cause channel inactivation. The results demonstrate that expression of different K+ channel genes can produce channel protein subunits that assemble as heteromultimers with unique properties. It is shown that certain combinations of voltage-gated K+ channels probably do not contribute to native transient outward current. However, one combination of subunits could not be excluded. Therefore, this mechanism of channel assembly may underlie some of the functional diversity of potassium channels found in the cardiovascular system.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Potassium voltage-gated channel subfamily A member 4P22459Details
Potassium voltage-gated channel subfamily A member 2P16389Details