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Cloning and characterization of an Ito-like potassium channel from ferret ventricle
- Source :
- American Journal of Physiology-Heart and Circulatory Physiology. 267:H1383-H1395
- Publication Year :
- 1994
- Publisher :
- American Physiological Society, 1994.
-
Abstract
- FK1, a ferret ventricular full-length cDNA clone, encodes a 654-amino acid protein with 98% identity to human K+ transient outward current (Ito)-like HK1 (Tamkun et al. FASEB J.5: 331-337, 1991). FK1 is detectable in ferret brain, atrium, left and right ventricle, and kidney but not in skeletal muscle, endothelial cells, aorta, and liver. In Xenopus oocytes, FK1 cRNA gives rise to a rapidly activating and inactivating Ito-like current, which is highly K+ selective (Na(+)-to-K+ permeability ratio = 0.003). Activation occurs over an approximately 50-mV range (-40 to +10 mV) and displays a sigmoid delay in onset with potential-dependent time constants that decrease with depolarization. Steady-state activation can be described with either a simple Boltzmann relationship [half-activation potential (V1/2) = -25 mV, slope (k) = 10 mV] or a Boltzmann relationship raised to either the third or fourth power (alpha 3: V1/2 = -43 mV, kappa = 13.1 mV; alpha 4: V1/2 = -48 mV, kappa = 13.6 mV, where alpha is the activation variable). Inactivation kinetics are biexponential, with the main fast time constant becoming independent of membrane potential depolarized to 0 mV. Steady-state inactivation can be described with a single Boltzmann relationship (V1/2 = -57 mV, kappa = 5.0 mV). Fast inactivation is removed by NH2-terminal deletions. Recovery from inactivation (-90 mV) is quite slow (half-time = 4.8 +/- 2.5 s). In 2 mM extracellular K+ concentration ([K+]o), FK1 tail currents display conventional deactivation behavior; however, in 98 mM [K+]o the tail currents display "reopening" behavior. These results suggest a molecular basis for the electrophysiological similarities between ferret and human ventricular Ito (Campbell et al. J. Gen. Physiol. 101: 571-601, 1993; Nabauer et al. Circ. Res. 73: 386-394, 1993).
- Subjects :
- Male
DNA, Complementary
Potassium Channels
Transcription, Genetic
Physiology
Heart Ventricles
Xenopus
Molecular Sequence Data
Membrane Potentials
Physiology (medical)
medicine
Extracellular
Animals
Humans
Amino Acid Sequence
RNA, Messenger
Cloning, Molecular
DNA Primers
Gene Library
Membrane potential
Cardiac transient outward potassium current
Base Sequence
Sequence Homology, Amino Acid
Chemistry
Myocardium
Ferrets
Skeletal muscle
Depolarization
Anatomy
Recombinant Proteins
Potassium channel
Kinetics
Electrophysiology
medicine.anatomical_structure
Organ Specificity
Ventricle
Mutagenesis, Site-Directed
Oocytes
Biophysics
Female
Cardiology and Cardiovascular Medicine
Subjects
Details
- ISSN :
- 15221539 and 03636135
- Volume :
- 267
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Heart and Circulatory Physiology
- Accession number :
- edsair.doi.dedup.....2507e67a5e9e914c018a9bae5690c178