| Channels cycle between open and closed conformations. When open, a channelprovides a continuous pathway through the bilayer, allowing flux of many ions.
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Gramicidin is an example of a channel. It is an unusual peptide, with alternating D and L amino acids. In lipid bilayer membranes, gramicidin dimerizes and folds as a right handed b-helix. The dimer just spans the bilayer (See below and Fig. 20-11 p. 732).
The primary structureof gramicidin A: HCO-L-Val-Gly-L-Ala-D-Leu-L-Ala-D-Val-L-Val-D-Val-L-Trp-D-Leu-L-Trp-D-Leu-L-Trp-D-Leu-L-Trp-NHCH2CH2OH Note that the amino acids all have hydrophobic side-chains (R groups), D & L amino acids alternate, and both ends of the peptide are modified (blocked).
- The outer surface of the gramicidin dimer, which interacts with the core of the lipid bilayer, is hydrophobic.
- Ions pass through the more polar lumen of the helix.
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The 3D structure of gramicidin (solved via solid state NMR by J. Prilusky in 1996, Protein Databank file 1MAG) is displayed at right.
Right click the image to select "chain" from the color menu, and display as "sticks". Note the 2 gramicidin molecules joined head to head (via H-bonding at their formyl-N-termini). Drag the image to view the channel from the side, and down its axis.
View also with color CPK, and with spacefill display.
 Questions: Where are amino acid side-chains located in relation to the helix? (Hint: Look for Trp ring structures.) What is the significance of this location? What atoms line the helix lumen? How does the location of specific amino acids relative to the lipid bilayer, such as those with partly polar side-chains (e.g., tryptophan) and those with aliphatic side-chains, compare to the location of such residues in a typical transmembrane a-helix? Compare to the Chime exercise in the section on lipids & membranes.
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| Ion flow through individual gramicidin channels can be observed if a small number of gramicidin molecules is present in a lipid bilayer separating two compartments containing salt solution.
With transmembrane voltage clamped at some value, current (ion flow through the membrane) fluctuates. Each fluctuation, attributed to opening or closing of one gramicidin channel, is the same magnitude. The current increment corresponds to the current flow through a single channel. At right is a drawing - not actual data.
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| Gating (opening & closing) of a gramicidin channel is thought to involve reversible dimerization. An open channel forms when two gramicidin molecules join end to end to span the membrane. This model is consistent with the finding that, at high concentrations of gramicidin, the overall transport rate depends on [gramidicin]2.
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Cellular channels usually consist of large, protein complexes with multiple transmembrane a-helices. Their gating mechanisms must differ from that of gramicidin.
Control of channel gating is a form of allosteric regulation. Conformational changes associated with channel opening may be regulated by one of the following:
- Voltage
- Binding of a ligand (a regulatory molecule)
- Membrane stretch (e.g., via a link to the cytoskeleton)
| The technique of patch clamping is used to study ion channel activity.
A narrow bore micropipet containing a salt solution may be pushed up against a cell or vesicle (diagram A at right), and then pulled back, capturing a fragment of membrane across the pipet tip (B at right).
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| A voltage is imposed between an electrode inside the patch pipet and a reference electrode in contact with the surrounding salt solution. Current is carried by ions flowing through the membrane.
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| If a membrane patch contains a single channel with 2 conformational states, the current will fluctuate between 2 levels as the channel opens and closes, as represented below.
The increment in current, as the channel cycles between open and closed state,reflects the rate ofion fluxthrough asingle channel.
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View a videoof an oscilloscope image during a patch clamp recording.
Then carry out a Studio Exercise involving analysis of patch clamp data.
Интегрированное
календарно-тематическое планирование уроков истории в 11 классе
(2011-2012 учебный год)
Предмет: Всеобщая история и история России
Класс: 11А, 11Б
Количество часов в неделю: 2 часа
Учитель: Латыйпова Зухра Рафилевна
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| I семестр
| II семестр
| III семестр
| Всего
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| Количество часов
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| Количество контрольных работ
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| Количество практических работ
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Составлено в соответствии с учебной программой среднего (полного) общего образования по истории (базовый уровень), рекомендованной Министерством образования РФ и РБ, 2004 год.
Основная литература (УМК):
Всеобщая история: учебник «Новейшая история: XX век – начало XXI века. 11 класс». Базовый уровень», авт. Алексашкина Л.Н., Мнемозина, 2005 год, методические рекомендации преподавания Всеобщей истории в 11 классе.
История России: учебник «Россия в ХХ веке. 10-11 класс. Базовый уровень», авт. ЛевандовскийА.А., Щетинов Ю.А., Просвещение, 2000 год; «История России 1945-2008. 11 класс», авт. А.А. Данилов, А.И. Уткин, А.В. Филиппов, методические рекомендации преподавания истории России в 11 классе.
Рассмотрено на заседании школьного методического объединения учителей истории МОБУ СОШ села Амзя
городского округа город Нефтекамск
