Analyzing the Anatomy of the Ferret

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The goals of this study were to describe the anatomy of the ferret SA node, and to characterize expression of ion channel transcripts within the node and surrounding regions. We choose ferrets for this study because the size of their SA node made them amenable to microscopic studies and future electrophysiological characterization. As we have shown, a second advantage of the ferret is that the anatomy of its SA node more closely resembles that of the human than the popular rabbit and mouse models. Finally, the availability of a sequence in the domestic ferret may ultimately lead to the development of transgenic ferrets, which will enable us to further investigate the role played by individual channels in the ferret SA node.

There are striking similarities in SA node architecture between the human and ferret {890, 1014, 1050, 1053, 1057, 1069, 1505, 2599, 5693, 10719}. Both show the presence of central nodal arteries surrounded by concentrically arranged small dark and large pale cells. In contrast, the rabbit SA node has no central nodal artery and no distribution of dark and lightly stained cells as seen in ferret and human {1043}. The physiological consequences of the ferret architecture are potentially important to understanding human physiology and pathophysiology. For example, changes in intravascular pressure in the SA nodal artery should affect heart rate in the ferret but not rabbit {1042}. The differences in morphology could be indicative of different cells types expressing a different array of ion channels. The combination of central nodal arteries and distribution of dark and light cells that are similar to that described for the human SA node led us to suggest that the location and expression levels of ion ch...

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...ies in patients with sinus bradycardia resulting from genetic mutations or in mice resulting from knock out of a gene encoding a specific ion channel {7369, 7748, 8033, 9136, 9382, 8733}. Alternatively, the negative chronotropic effects of K+, Na+ and Ca2+channel blockers can also slow the heart rate. In addition, the negative chronotropic effects of TTX on the spontaneous heart rate of the isolated mouse heart, led to the identification of TTX-sensitive Na channels (brain type) in the mouse SA node {8033} We have documented their presence in the ferret SA node. Finally, if our findings are substantiated in the human heart, we believe that the widespread distribution of Na channels is functionally important. In patients with diseased SA node, Class I antiarrhythmic drugs could further impair the propagation of impulses out of the SA node to the crista terminalis.

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