Calcium inward current

In experiments using oxidant stress induced by the photoactivation of rose bengal (10 nM), a 75% decline in the calcium inward current was observed after 10 min, with only a sUght acceleration in the inactivation kinetics of the current (Shattock etal., 1990). However, this decline in the calcium inward current appears to occur secondary to an oxidant stress-induced calcium overload and not as... 

L-type or high-voltage-activated calcium channels carry the majority of the calcium inward current in smooth muscle cells. They start to activate at a high membrane potential (around -30 mV) with a maximum at slightly positive membrane potentials (around -f-10 mV), have a large conductance (20-25 pS with 110 mM Ba2+ as charge carrier), inactivate slowly, and are readily and specifically blocked by the classic organic calcium channel blockers nifedipine (a 1,4-dihydro-pyridine), verapamil (a phenylalkylamine), and dil-tiazem (a benzothiazepine) (see Hofmann etah, 1994). 

Agents that have no perceived action on the slow calcium inward current in the myocardium (voltage clamp) consist of the (hphenylpiperazines, and include cinnarizine and flunarizine. 

The studies of Bhatnager et al. (1990) and Beresewicz and Horackova (1991) also report a significant and important increase in the inward movement of Na through the TTX-sensitive Na channel in cells exposed to oxidant stress. It is likely that this increased inward current may play a role in prolonging the action potential and in loading the cell with sodium. Both of these effects would combine to create a situation that would tend to load the cell with calcium through alteration in the activity of the Na/Ca exchange mechanism (Matsuura et al., 1991). 

As with the effects of oxidant stress on the calcium channel, part of the change in the steady-state background current could also be attributed to an indirect effect secondary to the elevation of intracellular calcium (Matsuura and Shattock, 1991b). However, oxidant stress also exerted a direct effect on the inward rectifying potassium current (7ki). The combination of an inhibition of 7ki and the activation of a calcium-dependent current are likely to contribute to the prolongation of the action potential duration and the increased susceptibility... 

In addition to modification of calcium influx/efflux, other mechanisms like inhibition of slow inward current [363] and nickel-calcium exchange [364] have been suggested to explain the positive inotropic effects of nickel. Moreover, these inotropic effects might be mediated by an action of nickel on the outside surface of the cardiac cell membrane, where nickel inhibits the ATP-dependent component of the calcium extrusion, thereby causing contraction-enhancement [364, 365],... 

Fig. 2. Effect of calcium antagonists (CA) on a cardiac cell. Top typical cardiac action potential. The calcium (slow) inward current flows during the characteristic plateau phase (phase 2) of the action potential. This calcium influx is selectively inhibited by CA. Activation of the sarcoplasmic reticulum (SR) and other cellular calcium pools occurs via Ca + and Na+ ions which flow into the cell. The SR and other pools donate activator Ca + ions which stimulate the contractile proteins. The presence of tubular systems (invaginations), which are characteristic of cardiac tissues, results in considerable enlargement of the cellular surface, thus enabling an effective influx of Na+ and Ca + ions. Inhibition of the calcium inward flux by a CA causes diminished activation of the contractile proteins.

Fast Inward Sodium Current L Type Calcium Current Transient Outward Current Sodium-Calcium Exchange Current ATP Sensitive Potassium Current Inward Rectifying Potassium Current Delayed Rectifying Potassium Current... 

Amiodarone decreases the slope of phase 4 depolarization. The rate of spontaneous discharge of the sinoatrial node is increased by amiodarone as well as by its metabolite, desethylamiodarone. The depressant action of amiodarone on sinoatrial pacemaker function is, in addition to p-receptor blockade, related to an inhibition of the slow inward current carried by the calcium ion. 

Tse FW, Tse A (1999) a-Latrotoxin stimulates inward current, rise in cytosolic calcium concentration, and exocytosis in pituitary gonadotropes. Endocrinology 140 3025-33 Tzeng MC, Cohen RS, Siekevitz P (1978) Release of neurotransmitters and depletion of synaptic vesicles in cerebral cortex slices by a-latrotoxin from black widow spider venom. Proc Natl Acad Sci U S A 75 4016-20... 

The Class IV drugs are calcium channel blockers. They decrease the inward current carried by calcium, resulting in a decrease in the rate of Phase 4 spontaneous depolarization and slowed conduction in tissues dependent on calcium currents, such as the AV node (Figure 17.12). Although voltage-sensitive calcium channels occur in many different tissues, the major effect of calcium-channel blockers is on vascular smooth muscle and the heart. 

Metarhodopsin 11 activates transducin, leading to an exchange of bound GDP for GTP several hundred molecules of transducin are activated by a single molecule of metarhodopsin 11 within a fraction of a second. Transducin-GTP binds to, and activates, GMP phosphodiesterase, lowering the intracellular concentration of cGMP. As cGMP falls, a cation channel in the membrane closes, thus interrupting the steady inward current of sodium and calcium ions. This leads to hyperpolarization of the membrane and reduced secretion of neurotransmitter (Baylor, 1996). 

The main effect of adrenergic stimulation is to enhance the intracellular adenylyl cyclase activity. This in turn increases cyclic adenosine monophosphate levels. Protein kinase A is activated which modulates, i.e. phosphorylates, calcium and potassium channels. Phosphorylation of the calcium channel increases the inward current leading to early after-depolarization. 

As just outlined, both impulse initiation (automaticity) and conduction result from changes in the permeability of the external membrane of cardiac cells to various ions. Normally, impulse propagation in most cardiac cells results from a rapid but brief increase in sodium permeability which permits an influx of that ion and produces rapid depolarization. As cells become partially depolarized, either as a result of the normal "fast" sodium inward current or for other reasons, other changes in membrane permeability occur leading to a more slowly developing and smaller inward ion flow composed primarily of calcium. In diseased and/or partially depolarized cells this "slow" calcium current may be the only mechanism available for impulse propagation. It may also be responsible for impulse initiation in areas not normally automatic. 

Figure 2. A. Recording of calcium variations in a photocyte cluster of O. aranea. (i) 200mM KCl stimulation, ( (>) rinsing with ASW. Values are expressed as a ratio between Ca bound fura-2 and free fura-2. B. Whole cell patch-clamp recording on O. californica photocyte. Stimulation protocol holding potential of-lOOmV, steps of 25mV from -lOOmV to -i-lOOmV (a) outward current, (b) inward current...

Quantitatively, the binding of Ca2+ to the glycocalyx is of secondary importance compared to that bound by phospholipid elements. The glycocalyx does play a significant role in the determination of myocardial cell Ca2+ permeability (20, 21). Upon arrival of the appropriate electrical stimulus T ction potential), Ca2+ crosses the sarcolemma and is the principal cation responsible for a current called the "slow inward current" (lsi) (3-2, 22, 23, 24). Calcium is conducted across the sarcolemma through channels or pores which are controlled by the phosphorylation of sarcolemmal and sarcotubular proteins. Cardiac sarcolemma and sarcoplasmic reticulum are phosphorylated by exogenous and endogenous cyclic adenosine 5 -5 - monophosphate (cAMP)-dependent protein kinases (25, ... 

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