Ca2+ current

Opioids G-protein coupled p-, 5-, k-receptors l cAMP l Ca2+ currents t K+ currents l Excitability of peripheral and central neurons l Release of excitatory neurotransmitters p, 5 sedation, nausea, euphoria/re-ward, respiratory depression, constipation k dysphoria/aversion, diuresis, sedation... 

Annexins form an evolutionary conserved family of Ca2+ and phospholipid binding proteins implicated in membrane trafficking and the regulation of Ca2+ currents across membranes. 

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). 

On the other hand, some receptors are truly promiscuous in that they can activate two or more G-proteins from quite different classes, even in their normal cellular environment. For example, similar concentrations of thyroid-stimulating hormone (TSH 0.1-100 U/ml) can stimulate the incorporation of 32P-GTP into a, aQ, a12, a13, as, and aq/11 through activation of the thyrotropin receptor in membranes from human thyroid gland. TRH activation of Ca2+ currents in GH3 cells is obtunded equally by antisense-depletion of l2, aa, and aq/11, but not of aQ. Some individual genotypic P2y nucleotide receptors can also couple with equal affinity to PTx-sensitive and PTx-insensitive G-proteins in sympathetic neurons. The degree, or otherwise, of such promiscuity is presumably determined by the structure of the receptor protein itself. 

As an example of dual a- and (5y-mediated effects, one might consider the inhibition of N-type Ca2+ currents in sympathetic neurons by acetylcholine (Figures 7.11 and 7.12 see also Hille, 1994). Acetylcholine inhibits these currents through two different muscarinic receptors (M, and M4), using two different G-protein pathways. 

Mogul, D. J., Adams, M. E. Fox, A. P. (1993). Differential activation of adenosine receptors decreases N-type but potentiates P-type Ca2+ current in hippocampal CA3 neurons. Neuron 10 (2), 327-34. 

FIGURE 10-7 The delay between Ca2+ influx into the nerve terminal and the postsynaptic response is brief. The temporal relationships between the Ca2+ current and the action potential in the nerve terminal and the postsynaptic response in the squid giant synapse are shown. The rapid depolarization (a) and repolarization (b) phases of the action potential are drawn. A major fraction of the synaptic delay results from the slow-opening, voltage-sensitive Ca2+ channels. There is a further delay of approximately 200 is between Ca2+ influx and the postsynaptic response. (With permission from reference [20].)... 

Fry The voltage dependence of these STOCs that you have shown is interesting, because there is now more evidence for T type Ca2+ currents in smooth muscle cells. Kenton Sanders, you said that it was in the window current for the L-type Ca2+ channels, but it is probably about 10 mV too negative for that. Is there any evidence that T type channel activity will be involved ... 

Fagan KA, Mons N Cooper DMF 1998 Dependence of the Ca2+-mhibitable adenylyl cyclase of C6-2B glioma cells on capacitative Ca2+ entry. J Biol Chem 273 9297—9305 Fierro L, Parekh AB 2000 Substantial depletion of the intracellular Ca2+ stores is required for macroscopic activation of the Ca2+ release-activated Ca2+ current in rat basophilic leukaemia cells. J Physiol 522 247—257... 

Gilabert JA, Parekh AB 2000 Respiring mitochondria determine the pattern of activation and inactivation of the store-operated Ca2+ current Icrac- EMBO J 19 6401-6407 lino M 1990 Biphasic Ca2+ dependence of inositol 1,4,5-trisphosphate-induced Ca2+ release in smooth muscle cells of the guinea pig taenia caeci. J Gen Physiol 95 1103-1122 Iizuka K, Yoshii A, Dobashi K, Horie T, More M, Nakazawa T 1998 InsP3, but not novel Ca2+ releasers, contributes to agonist-initiated contraction in rabbit airway smooth muscle. J Physiol 511 915-933... 

Yao Y, Ferrer-Montiel AV, MontalM, TsienRY 1999 Activation of store-operated Ca2+current in Xenopus oocytes requires SNAP-25 and but not a diffusible messenger. Cell 98 475 485... 

Cheng H, Lederer WJ, Cannell MB 1993 Calcium sparks elementary events underlying excitation—contraction coupling in heart muscle. Science 262 740—744 Collier ML, Thomas AP, Berlin JR 1999 Relationship between L-type Ca2+ current and unitary sarcoplasmic reticulum Ca2+ release events in rat ventricular myocytes. J Physiol (Lond)... 

McHale We can record a Ca2+-activated K+ current within 10 ms of the upstroke of the L-type Ca2+ current in the presence of 20 mM EGTA. I don t know whether this is direct activation of the channel. 

ZhuGe R, Fogarty KE, Tuft RA, Lifshitz LM, Sayar K, Walsh JV 2000 Dynamics of signaling between Ca2+ sparks and Ca2+-activated K+ channels studied with a novel image-based method for direct intracellular measurement of ryanodine receptor Ca2+ current. J Gen... 

Kotlikojf It is also common not to be able to resolve the rise in cytosolic Ca2+ from a short, triggered Ca2+ current. But you can see the release. Presumably this... 

Nelson One of the things that happens when cells are isolated is that the Ca2+ channels run down or become non-functional. For this reason it is important to ensure that you have a robust Ca2+ current. Dr Isenberg has done this. If you have good Ca2+ current you should see a nice change in global Ca2+ as you depolarize. In your experiment, did you measure the Ca2+ currents under voltage clamp to see what type of Ca2+ current was being delivered to the cell ... 

Holton Those experiments were by Imaizumi and as I recollect the inward Ca2+ current was about 100 picoamps in that cell. One problem is that the Ca2+-activated K+ current is a lot bigger, in the order of nanoamps. Therefore the Ca2+ current is not very obvious. 

Nelson Why doesn t the Ca2+ current go across the whole cell ... 

Isenberg I would like to ask about the time relationship between the Ca2+ currents and the SK channel activity. Is there a delay ... 

Nelson The action potentials here are quite brief, and the BK channels are contributing to the repolarization. In fact, in order to obtain a decent estimate of the Ca2+ current amplitude we have to first block the BK channels. 

Ganitkevich VY, Isenberg G 1995 Efficacy of peak Ca2+ currents (ICa) as trigger of sarcoplasmic reticulum Ca2+ release in myocytes from the guinea-pig coronary artery. J Physiol 484 ... 

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