Biochemical and physiological properties of K⁺ channel-associated AKR6A (Kvβ) proteins

Voltage-gated potassium (Kv) channels play an essential role in the regulation of membrane excitability and thereby control physiological processes such as cardiac excitability, neural communication, muscle contraction, and hormone secretion. Members of the Kv1 and Kv4 families are known to associate with auxiliary intracellular Kvβ subunits, which belong to the aldo-keto reductase superfamily. Electrophysiological studies have shown that these proteins regulate the gating properties of Kv channels. Although the three gene products encoding Kvβ proteins are functional enzymes in that they catalyze the nicotinamide adenine dinucleotide phosphate (NAD[P]H)-dependent reduction of a wide range of aldehyde and ketone substrates, the physiological role for these proteins and how each subtype may perform unique roles in coupling membrane excitability with cellular metabolic processes remains unclear. Here, we discuss current knowledge of the enzymatic properties of Kvβ proteins from biochemical studies with their described and purported physiological and pathophysiological influences.