Membrane potential involving calcium

Fig. 4.1. Cellular model illustrating cell types in vascular wall involved in vasorelaxation induced by SERMs. Putative targets of SERMs are indicated within cyan tags. SERMs directly affect L-type VDCC, BK fil subunit in smooth muscle cells, and ER in endothelial cells. L-type VDCC L-type voltage-dependent calcium channel BK calcium-activated large conductance K+ channel PKG protein kinase G eNOS endothelial nitric oxide synthase GC soluble guanylate cyclase cGMP cyclic GM P V electrochemical membrane potential ER estrogen receptor. See text for further details...

Final repolarization (phase 3) of the action potential results from completion of sodium and calcium channel inactivation and the growth of potassium permeability, so that the membrane potential once again approaches the potassium equilibrium potential. The major potassium currents involved in phase 3 repolarization include a rapidly activating potassium current (Ikt) and a slowly activating potassium current (Iks)- These processes are diagrammed in Figure 14-3. 

In the myocardium, automaticity is the ability of the cardiac muscle to depolarize spontaneously (i.e., without external electrical stimulation from the autonomic nervous system). This spontaneous depolarization is due to the plasma membrane within the heart that has reduced permeability to potassium (K+) but still allows passive transfer of calcium ions, allowing a net charge to build. Automaticity is most often demonstrated in the sinoatrial (SA) node, the so-called pacemaker cells. Abnormalities in automaticity result in rhythm changes. The mechanism of automaticity involves the pacemaker channels of the HCN (Hyperpolarization-activated, Cyclic Nucleotide-gated) family14 (e.g., If, "funny" current). These poorly selective cation channels conduct more current as the membrane potential becomes more negative, or hyperpolarized. They conduct both potassium and sodium ions. The activity of these channels in the SA node cells causes the membrane potential to slowly become more positive (depolarized) until, eventually, calcium channels are activated and an action potential is initiated. 

Fig. 8. Effects of cannabinoids on synaptic transmission. Activation ofthe CBq receptor at the presynaptic axon terminal inhibits transmitter release from the synaptic vesicle. Three mechanisms can be involved in presynaptic inhibition X refers to unknown second messengers) inhibition of voltage-dependent calcium channels, activation of potassium channels and direct interference with the vesicle release machinery.TheCBi receptor can be activated by exogenous agonists, but also by the endocannahinoids anandamide (A 4) and 2-arachidonoylglycerol (2-AG i, which are released from the postsynaptic neuron by passive and/or facilitated diffusion. The synthesis of endocannahinoids is triggered by a depolarisation-induced ( / , membrane potential) calcium influx or by activation ofGq/n protein-coupled receptors...

Certain synthetic potassium channel openers have been shown to activate K a channels, such as NS-004 (Sargenteta/., 1993)andNS-1619. However, iberiotoxin was unable to reverse the functional effects of NS-004, and therefore its mechanism of action may also involve inhibition of calcium current rather than activation of K a channels. Some drugs (e.g., cro-makalim) that activate K -p channels have also been shown to activate K channels in aortic smooth muscle cells but not in other types of arterial smooth muscle. Since blockers of K a channels (charybdotoxin and <1 mM TEA+) had no effect on membrane potential hyperpolarizations or dilations to any of... 

At the dendritic level, GABA response is depolarizing because the chloride equilibrium potential is more positive than the membrane potential. Chloride ions and sodium or calcium ions may be involved in the response. The associated conductance increase is so large that the net result is inhibition because the membrane potential is clamped below the spike threshold. ... 

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