Slow influx

There is evidence that free hydroxyproline can be incorporated into collagen to some extent. Thus, Mitoma (26) found that free hydroxyproline was incorporated into chick embryo collagen at about 10% of the rate observed with proline. The scheme given above indicates a pathway by which there may be a relatively slow influx of hydroxyproline into the hydroxyproline intermediate. Similarly, the breakdown of this intermediate might be responsible for the formation of free hydroxyproline observed in some tissues and possibly also that found in urine. 

Purkinje cells is demonstrated in Figure 12.1 and, like all cardiac myocytes, can be divided into four phases. Phase 4 (pacemaker potential) involves the slow influx of sodium ions, depolarizing the cell until the threshold potential is reached. Once the threshold potential is reached, the fast sodium current is activated, resulting in a rapid influx of sodium ions causing cell depolarization (phase 0 rapid depolarization). Phase 1 (partial repolarization) involves the inactivation of sodium channels and a transient outward current. Phase 2 (plateau phase) results from the slow influx of calcium ions. Repolarization (phase 3) occurs as a result of outflow of potassium ions from the cell and restores the resting potential. There are variations between the different areas of the heart, specifically the nodal tissues do not possess fast sodium channels and slow L-t5rpe calcium channels generate phase 0 current (Fig. 12.1). Phase 4 activity varies between nodal areas the sinoatrial node depolarizes more rapidly than the atrioventricular (AV) node. Automaticity is under autonomic nervous system control. Parasympathetic neurons... 

Plateau phase in which a slow influx of Ca2+ (ICa.L) is balanced by a late-appearing outward K+ current (the delayed rectifier current IK). 

Chen, T.M. Abdelhameed, M.H. Chiou, W.L. Erythrocytes as a total barrier for renal excretion of hydrochlorothiazide slow influx and efflux across erythrocyte membranes. J.Pharm.Sci., 1992, 81,... 

There are two types of influx, namely (a) rapid influx b) slow influx. 

B. Slow Influx. The slow influx of Ca gets triggered off to equalize (balance) the loss besides maintaining a proper relative voltage plateau as shown in Fig. 11.1 (d). In fact, as the Ca entry slows down, the membrane potential becomes low very swiftly to the predepolarization levels (i.e., phase 4). Thus, in the heart muscle the electrical activity is coupled to a mechanical activity by Ca as the potential trigger. 

The T-channel and L-channel are widely distributed in the conductive system of the heart, especially the sinoatrial (SA) node. The first phase of cell depolarisation in the SA node will be started via the activation of the T-channel (allowing fast influx of extracellular calcitun ions), while the later phase of depolarisation will be controlled by the L-channel (slow influx). CCBs have no significant activity on the T-channel. Instead they shorten the L-channel opening time, which increases the penetration time required for Ca ions to completely depolarise the cell and hence this reduces the heart rate (negative chronotropic effect). 

When drilling through normally pressured formations, the mud weight in the well is controlled to maintain a pressure greater than the formation pressure to prevent the influx of formation fluid. Atypical overbalance would be in the order of 200 psi. A larger overbalance would encourage excessive loss of mud Into the formation, slow down... 

Calcium and Vascular Smooth Muscle Contraction. Calcium acts on a number of sites associated with the control of the cytoplasmic calcium concentration. Vascular smooth muscle contraction can be initiated by the opening of the slow calcium channel aUowing influx of extraceUular calcium through the sarcolemmal membrane into the cytoplasmic compartment. The iatraceUnlar calcium concentration increases to 1 x 10 Af, a threshold concentration necessary to initiate contraction. 

Verapamil (Table 1), the first slow channel calcium blocker synthesized to selectively inhibit the transmembrane influx of calcium ions into cells, lowers blood pressure in hypertensive patients having good organ perfusion particularly with increased renal blood flow. Sustained-release verapamil for once a day dosing is available for the treatment of hypertension. Constipation is a prominent side effect. Headache, dizziness, and edema are frequent and verapamil can sometimes cause AV conduction disturbances and AV block. Verapamil should not be used in combination with -adrenoceptor blockers because of the synergistic negative effects on heart rate and contractile force. 

The sinoatrial (SA) node is located in the wall of the right atrium near the entrance of the superior vena cava. The specialized cells of the SA node spontaneously depolarize to threshold and generate 70 to 75 heart beats/ min. The "resting" membrane potential, or pacemaker potential, is different from that of neurons, which were discussed in Chapter 3 (Membrane Potential). First of all, this potential is approximately -55 mV, which is less negative than that found in neurons (-70 mV see Figure 13.2, panel A). Second, pacemaker potential is unstable and slowly depolarizes toward threshold (phase 4). Two important ion currents contribute to this slow depolarization. These cells are inherently leaky to sodium. The resulting influx of Na+ ions occurs through channels that differ from the fast Na+ channels that cause rapid depolarization in other types of excitable cells. Toward the end of phase... 

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].)... 

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],... 

Phase 0 Spontaneous baseline drift results in the threshold potential being achieved at 40 mV. SlowL-type Ca2+ channels are responsible for further depolarization so you should ensure that you demonstrate a relatively slurred upstroke owing to slow Ca2+ influx. 

The primary objective of integration plot analysis is to analyze the data on influx of the test substrate from the circulating blood to the retina (i.e., blood-to-retina direction) across the BRB after intravenous administration of the test substrate. The advantage of this approach is that it allows reliable determination of the retinal uptake (i.e., clearance) of the test substrate which has a slow permeability across the BRB [28], On the other hand, due to the intravenous injection, interference by endogenous substrates and plasma-protein binding of the test substrate can produce an unseemingly low estimate of the retinal uptake. 

Interestingly, we have found that microbubble deflation in the ultrasound field is unusually slow for the microbubbles that contain perfluorocarbon gas when the surrounding medium is depleted of air and saturated with the same fluorocarbon gas [57]. So, perhaps in an air-saturated environment the ultra-sound-mediated destruction of microbubbles may depend on the influx of air into the bubbles, not just on the perfluorocarbon loss. 

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.

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