Developmental expression of a functional TASK-1 2P domain K+ channel in embryonic chick heart.
BACKGROUND
Background K+ channels are the principal determinants of the resting membrane potential (RMP) in cardiac myocytes and thus, influence the magnitude and time course of the action potential (AP).


METHODS
RT-PCR and in situ hybridization are used to study the distribution of TASK-1 and whole-cell patch clamp technique is employed to determine the functional expression of TASK-1 in embryonic chick heart.


RESULTS
Chicken TASK-1 was expressed in the early tubular heart, then substantially decreased in the ventricles by embryonic day 5 (ED5), but remained relatively high in ED5 and ED11 atria. Unlike TASK-1, TASK-3 was uniformly expressed in heart at all developmental stages. In situ hybridization studies further revealed that TASK-1 was expressed throughout myocardium at Hamilton-Hamburger stages 11 and 18 (S11 & S18) heart. In ED11 heart, TASK-1 expression was more restricted to atria. Consistent with TASK-1 expression data, patch clamp studies indicated that there was little TASK-1 current, as measured by the difference currents between pH 8.4 and pH 7.4, in ED5 and ED11 ventricular myocytes. However, TASK-1 current was present in the early embryonic heart and ED11 atrial myocytes. TASK-1 currents were also identified as 3 microM anandamide-sensitive currents. 3 microM anandamide reduced TASK-1 currents by about 58% in ED11 atrial myocytes. Zn2+ (100 microM) which selectively inhibits TASK-3 channel at this concentration had no effect on TASK currents. In ED11 ventricle where TASK-1 expression was down-regulated, IK1 was about 5 times greater than in ED11 atrial myocytes.


CONCLUSIONS
Functional TASK-1 channels are differentially expressed in the developing chick heart and TASK-1 channels contribute to background K+ conductance in the early tubular embryonic heart and in atria. TASK-1 channels act as a contributor to background K+ current to modulate the cardiac excitability in the embryonic heart that expresses little IK1.
Zhang
Hengtao
H
The George and Jean Brumley, Jr, Neonatal-Perinatal Research Institute, Division of Neonatology/Department of Pediatrics, Duke University Medical Center, Box 2635, Durham, NC 27710, USA. zht@duke.edu
Parker
Jeremy
J
Shepherd
Neal
N
Creazzo
Tony L
TL
D000595:Amino Acid Sequence; D000818:Animals; D002642:Chick Embryo; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology*; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D032342:Muscle Cells / Q000166:cytology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000737:chemistry*; D015221:Potassium Channels / Q000096:biosynthesis* / Q000737:chemistry*; D024683:Potassium Channels, Tandem Pore Domain / Q000096:biosynthesis* / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
C407082:Kcnk9 protein, rat; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; C420132:potassium channel subfamily K member 3