Submitted on January 18, 2006
Accepted on March 27, 2006
Electrophysiological Characterization of Murine HL-5 Atrial Cardiomyocytes
Yong-Fu Xiao1*, Erica M. TenBroek2, Joshua J. Wilhelm1, Paul A. Iaizzo3, and Daniel C. Sigg1
1 Cardiac Rhythm Disease Management, Medtronic Inc, Minneapolis, Minnesota, United States
2 Corporate Science and Technology, Medtronic Inc, Minneapolis, Minnesota, United States
3 Departments of Surgery and Physiology, University of Minnesota, Minneapolis, Minnesota, United States
* To whom correspondence should be addressed. E-mail: yong-fu.xiao{at}medtronic.com.
HL-5 cells are cultured murine atrial cardiomyocytes and have been used in studies to address important cellular and molecular questions. However, electrophysiological features of HL-5 cells have not been characterized. Here, we examined such properties by using whole-cell patch-clamp techniques. Membrane capacitance of the HL-5 cells was from 8 to 62 pF. The resting membrane potential was -57.8 ± 1.4 mV (n = 51). Intracellular injection of depolarizing currents evoked action potentials (APs) with variable morphologies in 71% of the patched cells. Interestingly, the incidence of successful, current-induced APs positively correlated with the hyperpolarizing degrees of resting membrane potentials (r= 0.99, p < 0.001). Only a few of the patched cells (4 of 51, 7.8%) exhibited spontaneous APs. The muscarinic agonist carbachol activated the acetylcholine-activated K+ current (IK(ACh)) and significantly shortened the duration of APs. Immunostaining confirmed the presence of the muscarinic receptor type 2 (M2) in HL-5 cells. The hyperpolarization-activated cation current (If) was detected in 39% of the patched cells. The voltage (V1/2) to activate 50% of If channels was -73.4 ± 1.2 mV (n = 12). Voltage-gated Na+, Ca2+, and K+ currents were observed in the HL-5 cells with variable incidences. Compared with the adult mouse cardiomyocytes, the HL-5 cells had prolonged APs and small outward K+ currents. Our data indicate that HL-5 cells display significant electrophysiological heterogeneity of morphological appearance of APs and expression of functional ion channels. Compared with adult murine cardiomyocytes, HL-5 cells show an immature phenotype of cardiac AP morphology.
