Comparison of the single-cell properties of the guinea-pig and rabbit AV node

University of Leeds (2002) J Physiol 544P, S277

Research Symposium: Comparison of the single-cell properties of the guinea-pig and rabbit AV node

Jules C. Hancox* and Kathryn H. Yuill†

*Department of Physiology and Cardiovascular Research Laboratories, School of Medical Sciences, University Walk, Bristol BS8 1TD and †Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK

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Single-cell preparations have been used extensively to study action potential (AP) and pacemaker potential (PP) genesis in the sinoatrial (SA) and atrioventricular (AV) nodes of the heart. The location and complex morphology of the AV node has made single cell studies of this region a particular challenge. The morphological features of the AV node of the rabbit heart were well described in the 1970s (Anderson, 1972; Anderson et al. 1974) and, to date, data regarding the single-cell electrophysiology of the AV node have been derived exclusively from AV node cells isolated from this species. Taken collectively, the data from studies by a number of groups have shown that some electrophysiological properties of rabbit AV nodal cells resemble closely those reported for SA nodal cells from the same species, whilst other properties differ between the two regions. For example, in both SA and AV nodes, channels for inwardly rectifying K+ current (IK1) are scarce, if not entirely absent. Both cell types exhibit zero current potentials somewhat positive to the potassium equilibrium potential and cell input resistance is high, making membrane potential highly labile over the PP range. However, rabbit AV and SA nodal cells appear to differ in the delayed rectifier K+ current subtypes present since, under similar recording conditions, SA nodal myocytes exhibit both rapid and slow components (IKr and IKs, respectively), whilst AV nodal cells exhibit only IKr (Habuchi & Giles, 1995; Sato et al. 2000). Also, the density of the hyperpolarisation-activated ‘pacemaker’ current, If, appears to be greater in SA than in AV nodal myocytes (Habuchi & Giles, 1995).

In order to be able to place data from rabbit AV nodal cells into a wider context, comparative data are required from one or more other species. Recently, we have isolated Ca2+-tolerant single cells from the guinea-pig AV node and have begun to characterise their electrophysiological properties. Cell shapes and dimensions were comparable to those observed from rabbit AV nodal cells. Guinea-pig AV nodal cells exhibited small membrane capacitance values (~25 pF), a zero-current potential close to -40 mV and high input resistances (in excess of 1 GΩ). Whole-cell voltage-clamp experiments revealed a number of distinct current components. ICa,L exhibited a similar density to that observed previously in rabbit AV node cells (Hancox & Levi, 1994) and there was evidence for INa in some cells. In contrast with the rabbit AV node, there was no evidence for a transient outward K+ current. Delayed outward current comprised two components; these exhibited half-maximal activation voltages of -17.2 and +27.1 mV, suggesting that both IKr and IKs are present the guinea-pig AV node. At negative voltages, net inward current could be separated into three components, two of which were If and a background current. Surprisingly, however, a barium-sensitive inwardly rectifying current was also evident at the start of applied voltage commands, and was prominent at potentials negative to the PP range. Our experiments on guinea-pig AV nodal cells demonstrate that differences exist between rabbit and guinea-pig in AV nodal single cell electrophysiology. Further comparative studies are now required in order to determine which AV nodal cellular properties are widely preserved across species, and also to establish the functional consequences of observed differences.

This work was sponsored by a research fellowship to J.C.H. from The Wellcome Trust.




Where applicable, experiments conform with Society ethical requirements.

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