We have examined the actions of Zn2+ ions on Shaker K channels. We found that low (100 microM) concentrations of Zn2+ produced a substantial (approximately three-fold) slowing of the kinetics of macroscopic activation and inactivation. Channel deactivation was much less affected. These results were obtained in the presence of 5 mM Mg2+ and 4 mM Ca2+ in the external solution and so are unlikely ...

Mutations of the pore-region residue T442 in Shaker channels result in large effects on channel kinetics. We studied mutations at this position in the backgrounds of NH2-terminal-truncated Shaker H4 and a Shaker -NGK2 chimeric channel having high conductance (Lopez, G.A., Y.N. Jan, and L.Y. Jan. 1994. Nature (Lond.). 367: 179-182). While mutations of T442 to C, D, H, V, or Y resulted in undetec...

Parthenolide (PTN), a selective nuclear factor kappa B (NF-κB) inhibitor, has been used extensively to inhibit NF-κB activation. The duration of the inhibitory effect of PTN on NF-κB in vivo remains unclear. This study was to determine whether a lipopolysaccharide (LPS) challenge 6, 12 and 24 h after the administration of PTN could activate NF-κB. Rats were devided into five groups. The rats in...

OBJECTIVES This study compared the effects of morning and evening dosing of amlodipine/valsartan combination on 24-h blood pressure (BP) in patients uncontrolled by amlodipine (5 mg). METHODS This was a multicenter study that used a prospective, randomized, open-label, blinded endpoint design. Patients with essential hypertension, who's ambulatory BP was uncontrolled after 4 weeks on amlodipi...

With increasing economic and social demands, we are rapidly evolving into a 24-h society. In any urban economy, about 20% of the population are required to work outside the regular 0800-1700 h working day and this figure is likely to increase. Although the increase in shiftwork has led to greater flexibility in work schedules, the ability to provide goods and services throughout the day and nig...

BACKGROUND Flutter VRP1, Shaker, and Acapella are devices that combine positive expiratory pressure (PEP) and oscillations. OBJECTIVES To compare the mechanical performance of the Flutter VRP1, Shaker, and Acapella devices. METHODS An experimental platform and a ventilator, used a flow generator at 5, 10, 15, 20, 26, and 32 L/min, were employed at angles of -30°, 0°, and +30° to evaluate Fl...

Substitution of the S4 of Shaw into Shaker alters cooperativity in channel activation by slowing a cooperative transition late in the activation pathway. To determine the amino acids responsible for the functional changes in Shaw S4, we created several mutants by substituting amino acids from Shaw S4 into Shaker. The S4 amino acid sequences of Shaker and Shaw S4 differ at 11 positions. Simultan...