- 作者: Hengtao Zhang, Jeremy Parker, Neal Shepherd, Tony L Creazzo
- 作者服務機構: The George and Jean Brumley, Jr, Neonatal-Perinatal Research Institute, Division of Neonatology/Department of Pediatrics, Duke The George and Jean Brumley, Jr, Neonatal-Perinatal Research Institute, Division of Neonatology/Department of Pediatrics, Duke University Medical Center, Durham, NC, USA University Medical Center, Box 2635, Durham, NC 27710, USA
- 中文摘要: --
- 英文摘要:
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 μM
anandamide-sensitive currents. 3 μM anandamide reduced TASK-1 currents by about 58% in ED11
atrial myocytes. Zn2+ (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.
Conclusion: 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. - 中文關鍵字: --
- 英文關鍵字: --