Cell excitability

Inward Rectifier Potassium Channels or Kir Channels are a class of potassium channels generated by tetra-meiic arrangement of one-pore/two-transmembrane helix (1P/2TM) protein subunits, often associated with additional beta-subunits. Kir channels modulate cell excitability, being involved in repolarization of action potentials (see Fig. 1), setting the resting potential (see Fig. 1) of the cell, and contributing to potassium homeostasis. 

Sodium channels open more rapidly than K+ channels because they are more voltage sensitive and a small depolarization is sufficient to open them. Larger changes in membrane potential associated with further cell excitation are required to open the less voltage-sensitive K+ channels. Therefore, the increase in the permeability of K+ ions occurs later than that of Na+ ions. This is functionally significant because if both types of ion channels opened concurrently, the change in membrane potential that would occur due to Na+ ion influx would be cancelled out by K+ ion efflux and the action potential could not be generated. 

FIGURE 6-1 Path of excitation in a simplified spinal reflex that mediates withdrawal of the leg from a painful stimulus. In each of the three neurons and in the muscle cell, excitation starts with a localized slow potential and is propagated via an action potential (a.p.). Slow potentials are generator potential (g.p.) at the skin receptor the excitatory postsynaptic potentials (e.p.s.p.) in the interneuron and the motoneuron and end-plate potential (e.p.p.) at the neuromuscular junction. Each neuron makes additional connections to other pathways that are not shown. 

In smooth muscle, the sarcoplasmic reticulum (SR) plays an important role in regulating cell excitability by communicating intimately with ion channels in the surface membrane. In most cases, Ca2+ release from ryanodine-sensitive Ca2+ release channels (RyRs) in the SR leads to a paradoxical decrease in smooth muscle cell excitability due to activation of plasma membrane K+ channels (Fig. 1 Nelson et al 1995). This is in stark contrast to cardiac muscle, where Ca2+ release from RyRs supplies the majority (> 90%) of Ca2+ required for contraction (Cheng et al 1993, Cannell et al 1995). In this paper, we will briefly review the basic... 

Besides these, type-lb arrhythmia can occur at 12-30 min after the onset of ischemia with a peak at 15-20 min. These type-lb arrhythmias are either due to a partial recovery of the cell excitability (partial recovery of dU/dt and of the action potential duration), which may be ascribed to the release of catecholamines [for review see, Janse and Wit, 1989] or are due to gap junctional... 

Morley GE, Anumonwo JMB, Delmar M Effects of 2,4-dinitrophenol or low [ATP on cell excitability and action potential propagation in guinea pig ventricular myocytes. Circ Res 1992 71 821-830. 

Gereau, R.W. 4th and Conn, P.J. Roles of specific metabotropic glutamate receptor subtypes in regulation of hippocampal CA1 pyramidal cell excitability, J Neurophysiol. 1995, 74, 122-129. 

B-81MI10607 B. Hendry Membrane Physiology and Cell Excitation , Croom Helm, London,... 

Tseng K. Y. and O Donnell P. (2004). Dopamine-glutamate interactions controlling prefrontal cortical pyramidal cell excitability involve multiple signaling mechanisms. J. Neurosci. 24 ... 

Cav 1.2 L-type CClC cardiac muscle, endocrine cells excitation-contraction coupling, hormone secretion DHPs lethal... 

Mueller, D., Porter, J. T. Quirk, G. J. (2008). Noradrenergic signaling in infralimbic cortex increases cell excitability and strengthens memory for fear extinction. J. Neurosci., 28, 369-375. 

The 5-HT2 family comprises three receptor types 5-HT2A, 5-HT2B, and 5-HT2C, which show a high sequence homology, the similarity between their transmembrane domains being above 70%. These receptors are positively coupled to phospholipase C and phospholipase A2 through the Gq-protein and their activation leads to cell excitation (see Chapters 12 and 13 for details). 

The theoretical results quoted here and below make use of the most recent calculations of the reduced mass and recoil corrections [30,31,32] and values of the fundamental constants (see [24,25]). We stress once more that systematic and random uncertainties due to the calibration procedure completely dominate the quoted experimental errors detailed examination of the data suggests that the total contribution from other sources is less than 50 kHz, despite the use of cell excitation and the need to extrapolate to... 

There are other obvious refinements. The Oxford experiments were carried out using commercial lasers, with frequency jitter around the 1 MHz level there are well established techniques which can reduce this substantially. Cell excitation must... 

As outlined in Chapter 3, cell excitability can in part be determined by the maintenance of gradients of Na+, K+ and CP ions. Differential plasma membrane (PM) permeabilities to such ions and the gradients of ion concentration contribute to the transmembrane potential difference (t tm), which is typically about —0.1 volt (V) (inside with respect to the outside). In addition, the cytosolic free concentration of Ca2+ is extremely low (0.1 pM in resting cells and about 10 pM in excited cells) as compared to concentrations of Na+, CP and K+ of about 10, 10 and 100 mM, respectively, in the cytosol and about 100, 100 and 10 mM, respectively, in the extracellular milieu. These huge ion gradients are maintained through the operation of ion pumps such as the adenosine 5 -triphosphate (ATP)-energized Ca2+ pump (Ca2+-ATPase) and the Na+ and K+ pump (Na+, K+-ATPase). 

Q12 Hypocalcaemia increases the excitability of nerve and muscle cells. It is associated with reduction of the threshold potential necessary for initiation of nerve impulses, and consequently cell excitation occurs following a slight stimulus. The resulting symptoms include prolonged muscle spasms, which can particularly affect the face and limbs, hyper-reflexia, clonic-tonic convulsions and laryngeal spasm, which could cause asphyxia. 

Excitable cells - nerve cells and the various types of muscle cells - have a prominent role in the physiological processes that are targeted by drug therapy. We will therefore spend some time looking at how electrical cell excitation works. 

Membrane potentials also exist across membranes within cells. An important example is the potential across the inner mitochondrial membrane, which is the major driving force of ATP synthesis. However, since the intracellular potentials don t have a prominent role in cell excitation and pharmacology, the following discussion will focus on the potentials that occur at the cytoplasmic membrane. 

Voltage-gated channels. The voltage-gated channels for K, Na and Ca are all involved in cell excitability. 

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