Increasing evidence suggests the involvement of hyperpolarization-activated cyclic nucleotide-gated sodium/potassium channels (HCNs) not only in cardiac and neural function, but also in more general physiological processes including acid-base and ammonia regulation. We have identified four different HCN paralogs/isoforms in the goldfish Carassius auratus (CaHCN1, CaHCN2b, CaHCN4a and CaHCN4b) as likely candidates to contribute to renal, branchial and intestinal acid-base and ammonia regulation in this teleost. Quantitative real-time PCR showed not only high mRNA abundance of all isoforms in heart and brain, but also detectable levels (particularly of CaHCN2b and CaHCN4b) in non-excitable tissues, including gills and kidneys. In response to an internal or external acid-base and/or ammonia disturbance caused by feeding or high environmental ammonia, respectively, we observed differential and tissue-specific changes in mRNA abundance of all isoforms except CaHCN4b. Furthermore, our data suggest that the functions of specific HCN channels are supplemented by certain Rhesus glycoprotein functions to help in the protection of tissues from elevated ammonia levels, or as potential direct routes for ammonia transport in gills, kidney, and gut. The present results indicate important individual roles for each HCN isoform in response to acid-base and ammonia disturbances.

越来越多的证据表明，超极化激活的环状核苷酸门控钠/钾通道（HCN）不仅参与心脏和神经功能，而且参与更广泛的生理过程，包括酸碱和氨调节。我们在金鱼Car鱼中鉴定出四种不同的HCN同源物/同工型（CaHCN1，CaHCN2b，CaHCN4a和CaHCN4b）可能有助于在这种硬骨鱼中促进肾脏，分支和肠道酸碱和氨的调节。实时定量PCR不仅显示了心脏和大脑中所有同工型的高mRNA丰度，而且还显示了在非兴奋性组织（包括腮和肾脏）中可检测到的水平（尤其是CaHCN2b和CaHCN4b）。分别响应由进料或高环境氨引起的内部或外部酸碱和/或氨干扰，我们观察到除CaHCN4b以外的所有同工型mRNA丰度的差异和组织特异性变化。此外，我们的数据表明，特定的HCN通道功能被某些恒河猴糖蛋白功能所补充，有助于保护组织免受氨水平升高的影响，或作为ammonia，肾脏和肠道中氨气运输的潜在直接途径。目前的结果表明，每个HCN亚型在响应酸碱和氨干扰方面均具有重要的个体作用。