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Acta Physiologica 2013; Volume 207, Supplement 694
92nd Annual Meeting of the German Physiological Society
3/2/2013-3/5/2013
Heidelberg, Germany
CHARACTERIZATION OF SINGLE HCN2 CHANNELS EXPRESSED IN XENOPUS OOCYTES
Abstract number: P267
Thon
1
*S.
, Schmauder
1
R., Benndorf
1
K.
1
University Hospital Jena / Institute of Physiologie II, Jena, Germany
Hyperpolarization-activated cyclic nucleotide-modulated (HCN) ion channels are pacemaker channels generating rhythmicity in specialized neurons and cardiomyocytes. The tetrameric channels are non-specific cation channels that are activated by hyperpolarizing voltage and modulated by the binding of cAMP to cyclic nucleotide binding domains in each of the four subunits. In mammalians four isoforms of HCN channels have been identified (HCN1-4). The single-channel conductance of HCN channels has been described first in native sino-atrial node cells from Dario DiFrancesco in 1986. A very small conductance of ~1 pS was determined which is unusually small for a voltage-gated cation channel. Surprisingly, in recombinant HCN2 channels a much larger conductance of ~35 pS has been reported (Michels et al., Circulation, 2005). Later Dekker and Yellen (J. Gen. Physiol., 2006) confirmed a small conductance of ~1.5 pS similar to that in the native channels but also provided evidence for a pronounced cooperative gating of multiple channels, a phenomenon that conflicts with the widely accepted assumption of an independent function of ion channels. We studied single channel currents of HCN2 channels in inside-out patches expressed in Xenopus oocytes. Our results confirm a small conductance of ~2 pS and, so far, do not support the idea of a pronounced cooperativity between the channels. We further show that cAMP increases the open probability but does not alter the single-channel conductance. In conclusion, HCN2 channels expressed in Xenopus oocytes develop an only small single-channel conductance, probably gate as individual channels, and are activated by cAMP via an increase of the open probability.
To cite this abstract, please use the following information:
Acta Physiologica 2013; Volume 207, Supplement 694 :P267