Properties of the hyperpolarization-activated current (If) in isolated mouse sino-atrial cells

Objective: We have investigated the properties of the hyperpolarization-activated (I-t) current in pacemaker cells from the mouse sino-atrial node (SAN). Methods: The I-f current was studied in cells isolated enzymatically from the SAN region of adult C57BL6/J mice. The whole-cell variation of the patch-clamp technique was employed to investigate the basic properties of I-f. Results: In mouse SAN cells, the I-f current density at -120 mV was 18 +/-2 pA/pF (n=23). 1, was not detected in cells showing atrial-like morphology that were also found in SAN preparations (n=7). I-f was blocked by 5 mM Cs', was inhibited by application of 5 muM acetylcholine, and was increased by 10 muM noradrenaline. The 1, current reversal potential was -31 +/-2 mV under physiological concentration of Na+ and K+ ions. Lowering the extracellular Na+ concentration reduced If amplitude, while increased when the extracellular K+ concentration was augmented. I-f voltage for half activation was -87 +/-1 mV (n=6). Conclusions: We conclude that the native I-f current in mouse SAN cells shows functional properties that are similar to If described in rabbit SAN tissue. This study opens the possibility of investigating the involvement of I-f in the regulation of heart rate in genetically modified mice. (C) 2001 Elsevier Science B.V. All rights reserved.