Abstract-The K ϩ channel mKv1.5 is thought to encode a 4-aminopyridine (4-AP)-sensitive component of the current I K,slow in the mouse heart. We used gene targeting to replace mKv1.5 with the 4-AP-insensitive channel rKv1.1 (SWAP mice) and directly test the role of Kv1.5 in the mouse ventricle. Kv1.5 RNA and protein were undetectable, rKv1.1 was expressed, and Kv2.1 protein was upregulated in homozygous SWAP hearts. The density of the K ϩ current I K,slow (depolarizations to ϩ40 mV, pA/pF) was similar in left ventricular myocytes isolated from SWAP homozygotes (17Ϯ1, nϭ27) and littermate controls (16Ϯ2, nϭ19). The densities and properties of I peak , I to,f , I to,s , and I ss were also unchanged. In homozygous SWAP myocytes, the 50-mol/L 4-AP-sensitive component of I K,slow was absent (nϭ6), the density of the 20-mmol/L tetraethylammonium-sensitive component of I K,slow was increased (9Ϯ1 versus 5Ϯ1, PϽ0.05), and no 100-to 200-nmol/L ␣-dendrotoxin-sensitive current was found (nϭ8). APD 90 in SWAP myocytes was similar to controls at baseline but did not prolong in response to 30 mol/L 4-AP. Similarly, QTc (ms) was not prolonged in anesthetized SWAP mice (64Ϯ2, homozygotes, nϭ9; 62Ϯ2, controls, nϭ9), and injection with 4-AP prolonged QTc only in controls (63Ϯ1, homozygotes; 72Ϯ2, controls; PϽ0.05). SWAP mice had no increase in arrhythmias during ambulatory telemetry monitoring. Thus, Kv1.5 encodes the 4-AP-sensitive component of I K,slow in the mouse ventricle and confers sensitivity to 4-AP-induced prolongation of APD and QTc. Compensatory upregulation of Kv2.1 may explain the phenotypic differences between SWAP mice and the previously described transgenic mice expressing a truncated dominant-negative Kv1.

Biofilms play a central role in the pathobiology of otitis media (OM), bronchitis, sinusitis, conjunctivitis, and pneumonia caused by nontypeable Haemophilus influenzae (NTHI). Our previous studies show that extracellular DNA (eDNA) and DNABII proteins are essential components of biofilms formed by NTHI. The DNABII protein family includes integration host factor (IHF) and the histone‐like protein HU and plays a central role in NTHI biofilm structural integrity. We demonstrated that immunological targeting of these proteins during NTHI‐induced experimental OM in a chinchilla model caused rapid clearance of biofilms from the middle ear. Given the essential role of DNABII proteins in maintaining the structure of an NTHI biofilm, we investigated whether any of the other nucleoid associated proteins (NAPs) expressed by NTHI might play a similar role, thereby serving as additional target(s) for intervention. We demonstrated that although several NAPs including H‐NS, CbpA, HfQ and Dps are present within the biofilm extracellular matrix, only the DNABII family of proteins is critical for the structural integrity of the biofilms formed by NTHI. We have also demonstrated that IHF and HU are located at distinct regions within the extracellular matrix of NTHI biofilms formed in vitro, indicative of independent functions of these two proteins.