Abstract
ABSTRACTNeck ventroflexion in cats has different causes; however, the most common is the hypokalemia associated with flaccid paralysis secondary to chronic renal failure. In humans, the most common causes of acute flaccid paralysis are hypokalemia precipitated by thyrotoxicosis and familial forms linked to mutations in sodium, potassium, and calcium channel genes. Here, we describe the sequencing and analysis of skeletal muscle ion channels in Felis catus that could be related to periodic paralyses in humans, contributing to the understanding of the genetic susceptibility to feline neck ventroflexion and paralysis. We studied genomic DNA from eleven cats, including five animals that were hyperthyroid with hypokalemia, although only one presented with muscle weakness, and six healthy control domestic cats. We identified the ion channel ortholog genes KCNJ2, KCNJ12, KCNJ14, CACNA1S and SCN4A in the Felis catus genome, together with several polymorphic variants. Upon comparative alignment with other genomes, we found that Felis catus provides evidence for a high genomic conservation of ion channel sequences. Although we hypothesized that neck ventroflexion in cats could be associated with a thyrotoxic or familial periodic paralysis channel mutation, we did not identify any previously detected human channel mutation in the hyperthyroid cat presenting hypokalemia. However, based on the small number of affected cats in this study, we cannot yet rule out this molecular mechanism. Notwithstanding, hyperthyroidism should still be considered as a differential diagnosis in hypokalemic feline paralysis.
Highlights
Ion channels are macromolecular protein complexes that are components of the cell membrane and are essentially important in different types of signaling, including transport, excitability, and conduction
Certain congenital disturbances affecting the skeletal muscle have been identified in humans and animals, such as disorders in calcium and potassium channels that can lead to paralysis and disorders in chloride channels that can lead myotonia; both paralysis and myotonia can originate from sodium and calcium channel disequilibrium
Familial hypokalemic periodic paralysis (FHypokPP) is an autosomal dominant disease associated with mutations in calcium channels CACNA1S (Cav1.1) and SCN4A (Nav1.4) (Kim et al, 2011; Sternberg et al, 1993), and sporadic/ thyrotoxic hypokalemic paralysis is related to mutations in KCNJ18 (Kir2.6) (Cheng et al, 2011; Maciel et al, 2011; Ryan et al, 2010; Silva et al, 2004; Wang et al, 2006), we approached principally these genes
Summary
Ion channels are macromolecular protein complexes that are components of the cell membrane and are essentially important in different types of signaling, including transport, excitability, and conduction. Familial hypokalemic periodic paralysis (FHypokPP) is an autosomal dominant disease associated with mutations in calcium channels CACNA1S (Cav1.1) and SCN4A (Nav1.4) (Kim et al, 2011; Sternberg et al, 1993), and sporadic/ thyrotoxic hypokalemic paralysis is related to mutations in KCNJ18 (Kir2.6) (Cheng et al, 2011; Maciel et al, 2011; Ryan et al, 2010; Silva et al, 2004; Wang et al, 2006), we approached principally these genes.
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