Strategies for studying permeation at voltage-gated ion channels

Voltage-dependent ion channels are presently thought to consist of several distinct functional regions: (a) activation gates, (b) inactivation gates, and permeation pathways. This chapter focuses on permeation pathways and may spur new ideas about experiments that use site-directed mutagenesis to probe the ion conduction pathway. Some hubris is required to attempt a survey of this field since individual families -- K^+, Na^+, or Ca^(2+) -- have been reviewed in detail (15, 68, 115, 127). My unified treatment is motivated by the structural similarity suggested by recent cDNA sequencing data on this group (see, for instance, 24). There have been many excellent previous treatments of ion channel permeation (6, 15, 34, 35, 51, 53, 68, 73, 74, 115, 127)

Henry A. Wallace to John D. Feerick

Letter from Vice President Henry A. Wallace to Dean John D. Feerick, regarding his scholarly article on presidential inability.https://ir.lawnet.fordham.edu/twentyfifth_amendment_correspondence/1009/thumbnail.jp

Evaluating the operations capability of Freedom's Data Management System

Three areas of Data Management System (DMS) performance are examined: raw processor speed, the subjective speed of the Lynx OS X-Window system, and the operational capacity of the Runtime Object Database (RODB). It is concluded that the proposed processor will operate at its specified rate of speed and that the X-Window system operates within users' subjective needs. It is also concluded that the RODB cannot provide the required level of service, even with a two-order of magnitude (100 fold) improvement in speed

OPPORTUNITIES FOR EFFECTIVE EXTENSION POLICY EDUCATION

Teaching/Communication/Extension/Profession,

EXTENSION ACCOUNTABILITY--AN 1862 PERSPECTIVE

Teaching/Communication/Extension/Profession,

Gain of function mutants: Ion channels and G protein-coupled receptors

Many ion channels and receptors display striking phenotypes for gain-of-function mutations but milder phenotypes for null mutations. Gain of molecular function can have several mechanistic bases: selectivity changes, gating changes including constitutive activation and slowed inactivation, elimination of a subunit that enhances inactivation, decreased drug sensitivity, changes in regulation or trafficking of the channel, or induction of apoptosis. Decreased firing frequency can occur via increased function of K+ or Cl- channels. Channel mutants also cause gain-of-function syndromes at the cellular and circuit level; of these syndromes, the cardiac long-QT syndromes are explained in a more straightforward way than are the epilepsies. G protein-coupled receptors are also affected by activating mutations