Referenced in: none

Automatically associated channels: HCN1

Title: Changes of HCN gene expression and I(f) currents in Nkx2.5-positive cardiomyocytes derived from murine embryonic stem cells during differentiation.

Authors: Shuichi Yano, Junichiro Miake, Einosuke Mizuta, Kasumi Manabe, Udin Bahrudin, Kumi Morikawa, Keita Arakawa, Norihito Sasaki, Osamu Igawa, Chiaki Shigemasa, Yasutaka Yamamoto, Takayuki Morisaki, Kyoko Hidaka, Yasutaka Kurata, Akio Yoshida, Goshi Shiota, Katsumi Higaki, Haruaki Ninomiya, Jong-Kook Lee, Yasuaki Shirayoshi, Ichiro Hisatome

Journal, date & volume: Biomed. Res., 2008 Aug , 29, 195-203

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/18724007

Abstract
Changes in the expression of hyperpolarization-activated cyclic nucleotide (HCN)-gated channels and I(f) currents during the differentiation of embryonic stem cells into cardiac cells remain unknown. We examined changes of HCN genes in expression and function during the differentiation of Nkx2.5-positive cardiac precursor cells derived from mouse ES cells using cell sorting, RTPCR, immunofluorescence and whole cell patch-clamp techniques. Cs(+)-induced inhibition of automaticity and transcription of HCN genes increased during differentiation. Expressions of Nkx2.5, a marker of cardiac progenitor cell, and Flk1, a marker of hemangioblast, were mutually exclusive. Messenger RNA and proteins encoded by HCN1 and 4 genes were predominantly observed in Nkx2.5-positive cells on day 15, although Flk1-positive cells did not express genes of the HCN family on that day. Cs(+)-induced prolongation of the cycle of spontaneous action potentials and I(f) currents were predominantly observed on day 15. These results suggested that a fraction of Nkx2.5-positive cardiac precursor cells was committed to pacemaking cells expressing I(f) channels predominantly encoded by HCN 1 and 4 genes.