No abstract

KCNQ/K7 channels form a slow noninactivating K current, also known as the M current. They activate in the subthreshold range of membrane potentials and regulate different aspects of excitability in neurons of the central nervous system. In spinal motoneurons (MNs), KCNQ/K7 channels have been identified in the somata, axonal initial segment, and nodes of Ranvier, where they generate a slow, noninactivating, K current sensitive to both muscarinic receptor-mediated inhibition and KCNQ/K7 channel blockers. In this study, we thoroughly reevaluated the function of up- and downregulation of KCNQ/K7 channels in mouse immature spinal MNs. Using electrophysiological techniques together with specific pharmacological modulators of the activity of KCNQ/K7 channels, we show that enhancement of the activity of these channels decreases the excitability of spinal MNs in mouse neonates. This action on MNs results from a combination of hyperpolarization of the resting membrane potential, a decrease in the input resistance, and depolarization of the voltage threshold. On the other hand, the effect of inhibition of KCNQ/K7 channels suggested that these channels play a limited role in regulating basal excitability. Computer simulations confirmed that pharmacological enhancement of KCNQ/K7 channel activity decreases excitability and also suggested that the effects of inhibition of KCNQ/K7 channels on the excitability of spinal MNs do not depend on a direct effect in these neurons but likely on spinal cord synaptic partners. These results indicate that KCNQ/K7 channels have a fundamental role in the modulation of the excitability of spinal MNs acting both in these neurons and in their local presynaptic partners.

Experienced cardiologists can usually recognize pathologic heart murmurs with high sensitivity and specificity, although nonspecialists with less clinical experience may have more difficulty. Harsh, pansystolic murmurs of intensity grade > or = 3 at the left upper sternal border (LUSB) are likely to be associated with pathology. In this study, we designed a system for automatically detecting systolic murmurs due to a variety of conditions and examined the correlation between relative murmur intensity and likelihood of pathology. Cardiac auscultatory examinations of 194 children and young adults were recorded, digitized, and stored along with corresponding echocardiographic diagnoses, and automated spectral analysis using continuous wavelet transforms was performed. Patients without heart disease and either no murmur or an innocent murmur (n = 95) were compared to patients with a variety of cardiac diagnoses and a pathologic systolic murmur present at the LUSB (n = 99). The sensitivity and specificity of the automated system for detecting pathologic murmurs with intensity grade > or = 2 were both 96%, and for grade > or = 3 murmurs they were 100%. Automated cardiac auscultation and interpretation may be useful as a diagnostic aid to support clinical decision making.