Potassium Channel: Difference between revisions

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==Function==
==Function==


&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; [[Potassium Channel]]'''s''' control cell membrane electric potentials by selectively allowing diffusion of K<sup>+</sup> across the membrane.<ref name="Zhou">PMID: 11689936</ref> K<sup>+</sup> Channels extend across the cell membrane, a 40Å thick lipid bilayer which ions cannot cross.<ref name="Doyle">PMID: 9525859</ref> Potassium homeostasis is crucial for nearly all living cells, but is particularly important for the correct function of neurons. Neurons produce electrical impulses known as action potentials, allow for cellular communication processes like neurotransmitter release or to initiate intercellular processes muscle contraction. At the onset of an action potential, sodium ions flood across the plasma membrane of neurons via sodium channels. The change in polarity of the plasma membrane caused by the sodium ion influx inactivates sodium channels. Potassium channels subsequently open allowing the selective diffusion of K<sup>+</sup> ions across the plasma membrane, returning the membrane polarity to neutral. After the action potential has passed, channels recreate the high potassium concentration within the cell in preparation for the next stiumulus.<ref>PMID:12721618</ref> Mutations in voltage-gated potassium channel KCNC3 have been linked with [[Neurodevelopmental Disorders|neurodevelopmental disorders]] and neurodegeneration.<ref>PMID: 16501573</ref>
&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; [[Potassium Channel]]'''s''' control cell membrane electric potentials by selectively allowing diffusion of K<sup>+</sup> across the membrane.<ref name="Zhou">PMID: 11689936</ref> K<sup>+</sup> Channels extend across the cell membrane, a 40Å thick lipid bilayer which ions cannot cross.<ref name="Doyle">PMID: 9525859</ref> Potassium homeostasis is crucial for nearly all living cells, but is particularly important for the correct function of neurons. Neurons produce electrical impulses known as action potentials, allow for cellular communication processes like neurotransmitter release or to initiate intercellular processes muscle contraction. At the onset of an action potential, sodium ions flood across the plasma membrane of neurons via sodium channels. The change in polarity of the plasma membrane caused by the sodium ion influx inactivates sodium channels. Potassium channels subsequently open allowing the selective diffusion of K<sup>+</sup> ions across the plasma membrane, returning the membrane polarity to neutral. After the action potential has passed, channels recreate the high potassium concentration within the cell in preparation for the next stiumulus.<ref>PMID:12721618</ref>  


&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Potassium channels possess two traits that are seemingly mutually exclusive. Firstly, potassium channels have exquisite selectivity, with an amazing 10,000 fold selectivity for K<sup>+</sup> ions over sodium ions. Considering the only difference by which potassium ions can be differentiated from sodium ions is potassium ions’ 1.33Å Pauling radius vs. Sodium’s .95Å radius, the selectivity of potassium channels is remarkable.<ref name="Doyle"/> Second, despite its remarkable selectivity, potassium channels allow for the transfer of K<sup>+</sup> ions across the cell membrane at a rate of nearly 10<sup>8</sup> per second, nearly at the diffusion rate limit.<ref name="Long">PMID: 18004376</ref> Potassium channels are able to achieve these remarkable feats due to its amazing structural architecture, which contains several features which not only can sense the voltage potential across a membrane, but also selectively ferry K<sup>+</sup> ions without any outside energy expenditure.  
&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Potassium channels possess two traits that are seemingly mutually exclusive. Firstly, potassium channels have exquisite selectivity, with an amazing 10,000 fold selectivity for K<sup>+</sup> ions over sodium ions. Considering the only difference by which potassium ions can be differentiated from sodium ions is potassium ions’ 1.33Å Pauling radius vs. Sodium’s .95Å radius, the selectivity of potassium channels is remarkable.<ref name="Doyle"/> Second, despite its remarkable selectivity, potassium channels allow for the transfer of K<sup>+</sup> ions across the cell membrane at a rate of nearly 10<sup>8</sup> per second, nearly at the diffusion rate limit.<ref name="Long">PMID: 18004376</ref> Potassium channels are able to achieve these remarkable feats due to its amazing structural architecture, which contains several features which not only can sense the voltage potential across a membrane, but also selectively ferry K<sup>+</sup> ions without any outside energy expenditure.  


&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; The overall structure of the voltage gated potassium channel can be seen in the image at the left. It is comprised of 4 identical subunits and contains several key features which will be analyzed. Primarily, a <scene name='Potassium_Channel/Trans/3'>transmembrane region</scene> marked between the parallel lines in the figure. This region houses the <scene name='Potassium_Channel/Pore_opening/5'>channel pore</scene>, composed of interwoven helices in a teepee conformation, the all-important <scene name='Potassium_Channel/Selectivity_filter_opening/2'>“selectivity filter”</scene>, providing  the channel with its remarkable 10,00 fold selectivity for K<sup>+</sup> ions over Na<sup>+</sup> ions and the <scene name='Potassium_Channel/Voltage_sensors_opening/4'>“voltage sensor”</scene> which is uses well placed arginine and acidic residues to determine the membrane polarity and open/close the channel in response.<ref name="Long"/>
&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; The overall structure of the voltage gated potassium channel can be seen in the image at the left. It is comprised of 4 identical subunits and contains several key features which will be analyzed. Primarily, a <scene name='Potassium_Channel/Trans/3'>transmembrane region</scene> marked between the parallel lines in the figure. This region houses the <scene name='Potassium_Channel/Pore_opening/5'>channel pore</scene>, composed of interwoven helices in a teepee conformation, the all-important <scene name='Potassium_Channel/Selectivity_filter_opening/2'>“selectivity filter”</scene>, providing  the channel with its remarkable 10,00 fold selectivity for K<sup>+</sup> ions over Na<sup>+</sup> ions and the <scene name='Potassium_Channel/Voltage_sensors_opening/4'>“voltage sensor”</scene> which is uses well placed arginine and acidic residues to determine the membrane polarity and open/close the channel in response.<ref name="Long"/>
==Disease==
Mutations in voltage-gated potassium channel KCNC3 have been linked with [[Neurodevelopmental Disorders|neurodevelopmental disorders]] and neurodegeneration.<ref>PMID: 16501573</ref>. [[Amiodarone]] is a potassium channel blocker used in treatment of cardiac dysrhythmias.


==Selectivity Filter and Pore==
==Selectivity Filter and Pore==
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'''Potassium channels''' (KCh) are subdivided into voltage-gated KCh and calcium-dependent KCh.  The latter are subdivided into high- (BK, LKCa), intermediate- and small-conductance KCh (human SK1, rat SK2, SKCa).  The T1 domain is a highly conserved N-terminal domain which is responsible for driving the tetramerization of the KCh α subunit.  The inward rectifier KCh (IRK) passes current more easily in the inward direction.  KCh is activated by PIP2 [[Phosphatidylinositol bisphosphate (PIP2)]].MthK is a calcium-dependent KCh from ''Methanobacterium thermoautrophicum''.
'''Potassium channels''' (KCh) are subdivided into '''voltage-gated KCh''' and '''calcium-dependent KCh'''.  The latter are subdivided into '''high-''' (BK, LKCa), '''intermediate-''' and '''small-conductance KCh''' (human SK1, rat SK2, SKCa).  The '''T1 domain''' is a highly conserved N-terminal domain which is responsible for driving the tetramerization of the KCh α subunit.  The '''inward rectifier KCh''' (IRK) passes current more easily in the inward direction.  KCh is activated by [[Phosphatidylinositol bisphosphate (PIP2)]]. '''MthK''' is a calcium-dependent KCh from ''Methanobacterium thermoautrophicum''.  '''TMEM175''' or '''transmembrane protein 175''' is a KCh in lysosomes essdenial for their acidity<ref>PMID:37524211</ref>.  


== 3D structures of Potassium Channels==
== 3D structures of Potassium Channels==