Inward Rectifier K+ Channels

Inwardly Rectifying K+ Channels Voltage-dependent Na+ Channels... 

Inwardly Rectifying K+ Channels ATP-dependent K+ Channels Voltage-dependent Ca2+ Channels Ryanodine Receptor Voltage-dependent Na2+ Channels... 

Voltage-dependent Na+ Channels Nicotinic Receptors Ionotropic Glutamate Receptors Voltage-gated K+ Channels Inward Rectifier K+ Channels... 

Inward Rectifier K+ Channels Galanin Receptors Muscarinic Receptors... 

Inward Rectification refers to decreased conductance upon membrane depolarization. In classical inward rectifier K+ channels, rectification is strong and currents rapidly decline at membrane potentials positive to the reversal potential, in contrast to other Kir channels in which rectification is weak and currents decline only gradually at potentials positive to the reversal potential. 

Inwardly rectifying K+ channels Anomalous rectifiers Kir channels... 

Inward Rectifier K+ Channels. Figure 1 The role of inward rectifier (Kir) channels in cardiac action potentials. Depolarization is generated and maintained by Na and Ca currents (/Na, /Ca). Voltage-gated K currents (Kv) and Kir channels contribute to repolarization and maintenance of a negative resting potential. 

Inward Rectifier K+ Channels. Figure 2 High [K+] inside cells relative to outside results in normal rectification, whereby outward (positive by convention) potassium currents (/) when cells are depolarized (is positive relative to EK), are biggerthan inward (negative) currents at hyperpolarized (negative) voltages. Inward or anomalous rectifiers show strong or weak inward rectification whereby outward currents are smaller than inward currents. 

Inward Rectifier K Channels. Figure 4 Kir channel subunits consist of two transmembrane domains (M1, M2), separated by a pore loop (P-loop) that contains the signature K+-selectivity sequence (-GYG-), as well as extended cytoplasmic N - and C-termini. Several residues (indicated) have been implicated in causing rectification (see text). 

Inward Rectifier K+ Channels. Figure 5 Proposed three-dimensional arrangement of the transmembrane region of Kir channels. Two of four subunits are indicated. The pore consists of a selectivity filter close to the outside part of the membrane, a central inner vestibule, and a cytoplasmic entrance. Spermine may block in the inner cavity or in the selectivity filter. Large intracellular vestibule where polyamines may also block the channel is not shown. 

Inward Rectifier K+ Channels. Figure 6 Spermine (Amino-propyl-amino-butyl-amino-propyl amine) is a long linear naturally occurring polyamine containing four nearly equally spaced positively charged (at normal pH) amines. Although 16 A long, the molecule is only about 3 A wide, similar to a dehydrated potassium ion. 

The OP group of receptois share common effector mechanisms. All receptois couple via pertussis toxin-sensitive Go and Gi proteins leading to (i) inhibition of adenylate cyclase (ii) reduction of Ca2+ currents via diverse Ca2+ channels (hi) activation of inward rectifying K+ channels. In addition, the majority of these receptors cause the activation of phospholipase A2 (PLA2), phospholipase C 3 (PLC 3), phospholipase D2 and of MAP (mitogen-activated protein) kinase (Table 3). 

The inward rectifier K+ channels (Kir) represent this family of channels that conduct K+ ions preferentially in the inward direction than outward. The occlusion of internal vestibule oftheporeby Mg2+ and polyamines contribute to this inward rectification. These channels... 

Inward Rectifying K+ Channels Ionotropic Glutamate Receptors... 

Kd 50 nM for GIRK [G-protein-activated inwardly rectifying K+ channel] activation) and persistent in the absence of competing Ga-GDP, Py-effector binding is not irreversible. 

A G-protein-mediated effect has an absolute requirement for GTP. Reference has already been made to the requirement for GTP in reconstituting hormone-stimulated adenylate cyclase activity. A similar requirement can be demonstrated when the effector is an ion channel, such as the cardiac atrial inward-rectifier K+ channel which is activated following stimulation of the M2 muscarinic acetylcholine receptor. Thus, in the experiment illustrated in Figure 7.8, the channel recorded with a cell-... 

Parallel studies by Tallent et al. [65] have employed AtT-20 cells transfected with the fi receptor which couples to an endogenously expressed inwardly rectifying K+ channel. Prolonged application of DAMGO to these cells also desensitizes the ability of opiates to potentate the K+ current. The desensitization of the fi receptor in AtT-20 cells did not involve changes in the ability of the K+ channel to be activated since GTP analogs perfused into the opiate-treated cells increased K+ currents to a similar extent as in drug naive cells. 

Ma GH, Miller R, Kuznestov A et al. Kappa-opioid receptor activates an inwardly rectifying K+ channel by a G protein-linked mechanism coexpression in Xenopus oocytes. Mol Pharmacol 1995 47 1035-1040. 

Na+ channels were identified by neurotoxin labeling and their primary structures were established by cDNA cloning 101 Ca2+ channels have a structure similar to Na+ channels 103 Voltage-gated K+ channels were identified by genetic means 103 Inwardly rectifying K+ channels were cloned by expression methods 103... 

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