Biomedical subjects

Clay M Armstrong

Publications and source records attributed to Clay M Armstrong.

5 recordsLinked to original sources

PubMed2007

Life among the axons.

A blink in history's eye has brought us an understanding of electricity, and with it a revolution in human life. From the frog leg twitch experiments of Galvani and the batteries of Volta, we have progressed to telegraphs, motors, telephones, computers, and the Internet. In the same period, the ubiquitous role of electricity in animal and plant life has become clear. A great milestone in this journey was the elucidation of electrical signaling by Hodgkin & Huxley in 1952. This chapter gives a personal account of a small part of this story, the transformation of the rather abstract electrical conductances of Hodgkin & Huxley into the more tangible gated ion channel.

Animals↗

PubMed2006

Na channel inactivation from open and closed states.

A sodium channel is composed of four similar domains, each containing a highly charged S4 helix that is driven outward (activates) in response to a depolarization. Functionally, the channel has two gates, called activation gate (a gate) and inactivation gate (I gate), both of which must be open for conduction to occur. The cytoplasmically located a gate opens after a depolarization has activated the S4s of (probably) all four domains. The I gate consists of a cytoplasmically located inactivation "particle" and a receptor for it in the channel. The receptor becomes available after some degree of S4 activation, and the particle diffuses in to inactivate the channel. The I gate usually closes when the a gate is open [open-state inactivation (Osi)] but also can close before the channel reaches the conducting state. This "closed-state inactivation" (Csi) is studied quantitatively in this paper to determine the degree of S4 activation required for (i) opening the a gate, and (ii) permitting the I gate to close. Csi is most prominent for small depolarizations, during which occupancy of the partially activated closed states is prolonged. Large depolarizations drive the S4s outward quickly, minimizing the duration of closed-state occupancy and making Csi small and Osi large. Based on these data and evidence in the literature, it is concluded that opening the a gate requires S4 activation in domains 1-3, with partial activation of the S4 of domain 4. Csi requires only S4 activation of domains 3 and 4, which does not open the a gate.

Animals↗

PubMed2003

Voltage-gated K channels.

Ion channels and the electrical properties they confer on cells are involved in every human characteristic that distinguishes us from the stones in a field. Every perception, thought, movement, and heartbeat depends on electrical signals generated by the activity of ion channels. Early views of the relationship between channel structure and function have undergone substantial modification following the cloning of various ion channels and the determination of the structure of a simple bacterial K channel, the KcsA channel. This review focuses on the relationship between the structure and function of voltage-dependent K channels, covering the molecular bases of channel selectivity, conduction, and gating. The evolution of ion channels in bacteria is discussed, as well as the basis of channel selectivity and conduction in the KcsA channel. More complex channels have evolved molecular "gatekeepers," allowing them to respond to appropriate stimuli by opening, closing, and inactivating.

Animals↗

PubMed2003

The Na/K pump, Cl ion, and osmotic stabilization of cells.

An equation for membrane voltage is derived that takes into account the electrogenicity of the Na/K pump and is valid dynamically, as well as in the steady state. This equation is incorporated into a model for the osmotic stabilization of cells. The results emphasize the role of the pump and membrane voltage in lowering internal Cl(-) concentration, thus making osmotic room for vital substances that must be sequestered in the cell.

Animals↗

PubMed2002

Block of Shaker potassium channels by external calcium ions.

We describe an interaction between external Ca(2+) ions and Shaker K channels that is important in the gating of the channels. The interaction was first detected as a partial block of inward K(+) current in elevated Ca(2+), beginning near -40 mV and becoming stronger at more negative voltage. Surprisingly, the time course of the block can be resolved as a rapid decay of inward current magnitude following a repolarizing step. The rapid decay of current is shown to be the result of channel block by using a two-pulse procedure that monitors the time course of gate closing. As a result of block, the decay of the tail current after repolarization is two to three times faster than gate closing. With physiological values for voltage and calcium concentration, block is readily detectable from tail time course, implying that it occurs as a normal concomitant of gate closing in Shaker. The slight voltage dependence of block from -60 to -100 mV suggests that Ca(2+) is bound (with low affinity) near the outer mouth of the channel. Elevated calcium quickens the inward gating current recorded as Shaker channels are closing; this current approximately doubles in amplitude and has a faster time course and quicker rising phase. When combined, the results suggest that calcium accelerates the first step in closing of the channel gate, perhaps by changing the channel's ion-occupancy state.

Animals↗