Manipulation of KCNE2 expression modulates action potential duration and Ito and IK in rat and mouse ventricular myocytes.

In heterologous expression systems, KCNE2 has been demonstrated to interact with multiple α-subunits of voltage-dependent cation channels and modulate their functions. However, the physiological and pathological roles of KCNE2 in cardiomyocytes are poorly understood. The present study aimed to investigate the effects of bidirectional modulation of KCNE2 expression on action potential (AP) duration (APD) and voltage-dependent K(+) channels in cardiomyocytes. Adenoviral gene delivery and RNA interference were used to either increase or decrease KCNE2 expression in cultured neonatal and adult rat or neonatal mouse ventricular myocytes. Knockdown of KCNE2 prolonged APD in both neonatal and adult myocytes, whereas overexpression of KCNE2 shortened APD in neonatal but not adult myocytes. Consistent with the alterations in APD, KCNE2 knockdown decreased transient outward K(+) current (Ito) densities in neonatal and adult myocytes, whereas KCNE2 overexpression increased Ito densities in neonatal but not adult myocytes. Furthermore, KCNE2 knockdown accelerated the rates of Ito activation and inactivation, whereas KCNE2 overexpression slowed Ito gating kinetics in neonatal but not adult myocytes. Delayed rectifier K(+) current densities were remarkably affected by manipulation of KCNE2 expression in mouse but not rat cardiomyocytes. Simulation of the AP of a rat ventricular myocyte with a mathematical model showed that alterations in Ito densities and gating properties can result in similar APD alterations in KCNE2 overexpression and knockdown cells. In conclusion, endogenous KCNE2 in cardiomyocytes is important in maintaining cardiac electrical stability mainly by regulating Ito and APD. Perturbation of KCNE2 expression may predispose the heart to ventricular arrhythmia by prolonging APD.

Effect of lactase preparations in asymptomatic individuals with lactase deficiency--gastric digestion of lactose and breath hydrogen analysis.

We compared two lactase preparations derived from Aspergillus orizae (AOL) and Penicillinase multicolor (PML) for stability in the stomach and overall enzymatic activity in 10 asymptomatic subjects with lactase deficiency. The subjects were given 10,000 FCC units of either AOL or PML 30 min prior to or simultaneously with 300 ml of milk. Gastric juice was withdrawn through a nasogastric tube immediately after and every 15 min for 60 min, and breath was sampled before and every 15 min for 6 h after the milk ingestion. When lactase was given simultaneously with the milk, gastric juice lactase activity and galactose concentration were significantly higher than the control levels. When lactase preparations were given 30 min prior to the milk, neither lactase activity nor galactose was detected in the gastric juice. The pH of the gastric juice was about 6.0 after the milk ingestion. Breath hydrogen did not increase when milk was ingested simultaneously with enzymes, but did increase if enzymes were given 30 min prior to milk ingestion. There were no significant differences in lactase activity, galactose concentration in gastric juice, or breath hydrogen when AOL and PML were compared. In conclusion, with exogenous lactase, digestion of lactose begins in the stomach when pH is raised to 6.0 by the buffering action of milk. Lactase preparations are effective assessed by breath hydrogen analysis in asymptomatic individuals with lactase deficiency if the enzymes are given simultaneously with milk.