Cardiovascular pharmacology of K17.1 (TASK-4, TALK-2) two-pore-domain K channels.

K17.1 (TASK-4, TALK-2) potassium channels are expressed in the heart and represent potential targets for pharmacological management of atrial and ventricular arrhythmias. Reduced K17.

Physiological genomics identifies genetic modifiers of long QT syndrome type 2 severity.

Congenital long QT syndrome (LQTS) is an inherited channelopathy associated with life-threatening arrhythmias. LQTS type 2 (LQT2) is caused by mutations in KCNH2, which encodes the potassium channel hERG. We hypothesized that modifier genes are partly responsible for the variable phenotype severity observed in some LQT2 families.

Contribution of two-pore K channels to cardiac ventricular action potential revealed using human iPSC-derived cardiomyocytes.

Two-pore K (K) channels have been described in modulating background conductance as leak channels in different physiological systems. In the heart, the expression of K channels is heterogeneous with equivocation regarding their functional role. Our objective was to determine the K expression profile and their physiological and pathophysiological contribution to cardiac electrophysiology.

Identification of novel mouse genes conferring posthypoxic pauses.

Although central to the susceptibility of adult diseases characterized by abnormal rhythmogenesis, characterizing the genes involved is a challenge. We took advantage of the C57BL/6J (B6) trait of hypoxia-induced periodic breathing and its absence in the C57BL/6J-Chr 1(A/J)/NaJ chromosome substitution strain to test the feasibility of gene discovery for this abnormality. Beginning with a genetic and phenotypic analysis of an intercross study between these strains, we discovered three quantitative trait loci (QTLs) on mouse chromosome 1, with phenotypic effects.

Effects of hydrogen sulfide synthesis inhibitors on posthypoxic ventilatory behavior in the C57BL/6J mouse.

Background: H(2)S synthesis inhibitors (HSSI) have been shown to impact respiratory control. For instance, the HSSI hydroxylamine (HA) decreases the respiratory discharge rate from isolated medullary sections, and HA in addition to other HSSIs propargylglycine and amino-oxyacetic acid (AOAA) have been found to reduce hypoxic responsiveness.

Objectives: The aim of this study was to determine if administration of HSSIs could improve respiratory stability in an intact organism prone to recurrent central apneas.

Ventilatory behavior and carotid body morphology of Brown Norway and Sprague Dawley rats.

Differences in acute ventilatory behavior are associated with carotid body (CB) structural and immunohistologic profiles in some, but not all, reports. Brown Norway (BN) rats exhibit lower acute ventilatory responses to hypoxia and hypercapnia compared to Sprague Dawley (SD) rats. We hypothesized that BN rats possess CB with fewer glomus cells.

Morphological differences of the carotid body among C57/BL6 (B6), A/J, and CSS B6A1 mouse strains.

The C57/BL6 (B6) mouse strain exhibits post-hypoxic frequency decline and periodic breathing, as well as greater amount of irregular breathing during rest in comparison to the A/J and to the B6a1, a chromosomal substitution strain whereby the A/J chromosome 1 is bred onto the B6 background (Han et al., 2002; Yamauchi et al., 2008a,b).