Voltage-operated Ca2+ channels

Nimodipine A voltage-operated Ca2+ channel blocker with potential benefits in treating cognitive deficits and managing opiate and alcohol detoxification. 

Gu Y, Preston MR, Magnay J, El Haj AJ, Publicover SJ. 2001. Hormonally-regulated expression of voltage-operated Ca2+ channels in osteocytic (MLO-Y4) cells. Biochem Biophys Res Commun 282 536-42. 

Ca2+-induced Ca2+ release from ryanodine receptors caused by influx of Ca2+ through voltage-operated Ca2+ channels on the plasma membrane. 

When the action potential reaches the synaptic bouton, depolarisation triggers the opening of voltage-operated calcium channels in the membrane (Figure 2.5). The concentration gradient for Ca2+ favours the passive movement of this ion into the neuron. The subsequent rise in cytoplasmic Ca2+ ion concentration stimulates the release of neurotransmitter into the synaptic cleft, which diffuses across this narrow gap and binds to receptors located on the postsynaptic neuronal membrane (Figure 2.5). 

McCarron No, although we only have indirect evidence for this. Our reasoning is that the tonic component is blocked by inhibitors of the voltage-dependent Ca2+ channel, and it is not blocked by the SKF96365 which blocks store-operated channels. 

Increased Ca2+ influx through voltage-operated calcium channels (VOCCs) is... 

Figure 7.1. Diagrammatic representation of cellular Ca2 movements. Calcium ions (Ca2 ) may cross the sarcolemma by the following routes (7) voltage-operated calcium channels Q) receptor-operated calcium channels ( ) fast sodium channels (7) Ca2 -A TPase pump (J) Na -Ca2 exchange and Ca2 + leak pathways. Inside the cell, Ca2 may be taken up into and released from mitochondria (MIT) and sarcoplasmic reticulum (SR) (8). Ca2 also binds to the intracellular proteins, calmodulin and troponin C. REC represents a specific membrane receptor site.

All molecular systems involved in Ca2+ homeostatic processes are regulated by Ca2+ itself, which operates numerous feedback loops. That is, increase in cytosolic Ca2+ concentration induces a Ca2+-dependent inactivation of voltage-operated plasmalemmal Ca2+ channels. Fluctuations in [Ca2+]L differentially regulate Ca2+ transport across the endomembrane elevation of [Ca2+]L increases the susceptibility of RyRs and InsP3Rs to activation, and inhibits the SERCAs when [Ca2+]L falls, the SERCA pumping is much activated, and the Ca2+ release channels are inhibited (Burdakov et al., 2005 Burdakov and Verkhratsky 2006). 

In the calyx of Held synapse in the auditory brainstem of rats the 5-HTib receptor inhibition of glutamate release was fully explained by inhibition of Ca2+ entry through voltage-dependent channels (Mizutani et al. 2006). In rat nucleus accumbens, in contrast, the analogous 5-HTib effect did not involve inhibition of Ca2+ channels (Muramatsu et al. 1998). In rat amygdala, the 5-HTia inhibition operated via a cyclic AMP pathway and apparently inhibition of Ca2+ entry an unexplained observation was the failure of pertussis toxin to abolish the 5-HTia inhibition (Cheng et al. 1998). 

Kotlikoff Returning to the issue of receptor-operated or store-operated channels, one of the things I noticed in your traces was that your caffeine responses came back to baseline very smoothly. There was not the sustained elevation of [Ca2+] that you might predict. One of the things that is very different about voltage-clamped smooth muscle between a caffeine response and a phospholipase receptor-linked response is this additional current that is seen with the phospholipase receptor. I didn t see any functional evidence of a sustained response in your caffeine experiments. Have you voltage clamped these cells and looked to see whether there is any current there If not, do you think this is because the current is just too small to be able to measure ... 

Ca2+ enters cells via a number of plasma membrane channels which belong to three families (Figure 11.2) (i) voltage-gated channels (ii) ligand-gated channels and (iii) capacitative, or store-operated channels (SOCs). 

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