Developmental expression of a functional TASK-1 2P domain K channel in embryonic chick heartReportar como inadecuado




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Journal of Biomedical Science

, 16:104

First Online: 23 November 2009Received: 18 September 2009Accepted: 23 November 2009DOI: 10.1186-1423-0127-16-104

Cite this article as: Zhang, H., Parker, J., Shepherd, N. et al. J Biomed Sci 2009 16: 104. doi:10.1186-1423-0127-16-104

Abstract

BackgroundBackground 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.

MethodsRT-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.

ResultsChicken 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 and 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 μM anandamide-sensitive currents. 3 μM anandamide reduced TASK-1 currents by about 58% in ED11 atrial myocytes. Zn 100 μM 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.

ConclusionFunctional 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.

List of abbreviationsTASKTWIK-related Acid Sensitive Potassium Channels

RMPresting membrane potential

APAction Potential

EDEmbryonic Day

K2PTwo-pore Domain Potassium Channels

NTBNitro-Blue Tetrazolium Chloride

BCIP5-Bromo-4-Chloro-3-Indolyphosphate p-Toluidine Salt

TEATetraethylammonium

4-AP4-Aminopyridine

EGTAEthylene Glycol-bis β-aminoethyl ether N,N,N-N-tetraacetric acid

DMSOdimethylsulfoxide.

Electronic supplementary materialThe online version of this article doi:10.1186-1423-0127-16-104 contains supplementary material, which is available to authorized users.

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Autor: Hengtao Zhang - Jeremy Parker - Neal Shepherd - Tony L Creazzo

Fuente: https://link.springer.com/







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