The reduction of myocardial damage and leukocyte polymorphonuclear accumulation following coronary artery occlusion by the tyrosine kinase inhibitor tyrphostin AG 556

We investigated the effects of tyrophostin AG 556, a tyrosine kinase inhibitor, on the phenomenon of leukocyte accumulation during ischaemia and reperfusion of the myocardium. Male anaesthetized rats were subjected to total occlusion (45 min) of the left main coronary artery followed by 5 h reperfusion (MI/R). Sham myocardial ischaemia-reperfusion rats (Sham MI/R) were used as controls. Myocardial necrosis, myocardial myeloperoxidase activity (MPO), serum creatinine phosphokinase activity (CPK) serum Tumor Necrosis Factor (TNF-alpha) and Interleukin 6 (IL-6), cardiac intercellular adhesion molecule-1 (ICAM-1) and TNF-alpha expression and myocardial contractility (left ventricle dP/dt(max)) were evaluated. Myocardial ischaemia plus reperfusion in untreated rats produced marked myocardial necrosis, increased serum CPK activity (196.5 +/- 19 U/100 ml, at the end of reperfusion) and myeloperoxidase activity (MPO, a marker of leukocyte accumulation) both in the area-at-risk (4.5 +/- 0.5 U/g/tissue) and in necrotic area (8.2 +/- 1.2 U/g/tissue), reduced myocardial contractility (1,706 +/- 52 mmHg/s, at the end of reperfusion) and induced a marked increase in the serum levels of TNF-alpha (1,950 +/- 97 pg/ml, at 1 h of reperfusion) and IL-6 (998 +/- 16 U/ml, at the end of reperfusion). Finally, myocardial ischaemia-reperfusion injury also increased cardiac mRNA for TNF-alpha and ICAM-1 in the myocardium-at risk. Tyrphostin AG 556 (0.5, 1 and 2 mg/kg subcutaneously 5 min after the onset of reperfusion) lowered myocardial necrosis and myeloperoxidase activity in the area-at-risk (1.5 +/- 0.2 U/g/tissue, following the highest dose) and in necrotic area (2.9 +/- 0.3 U/g/tissue following the highest dose), decreased serum CPK activity (96 +/- 9 U/100 ml, at the end of reperfusion), lowered serum TNF-alpha and IL-6, increased myocardial contractility (2,096 +/- 88 mmHg s, at the end of reperfusion) and reduced cardiac mRNA levels for TNF-alpha and ICAM-1. The present data suggest that tyrosine kinase inhibitors protect against myocardial ischaemia-reperfusion injury by reducing leukocyte accumulation to the ischaemic myocardium.     

Further Study of the Electrical and Mechanical Responses of Slow Fibers in Cat Extraocular Muscles

Electrical and mechanical responses have been obtained in situ and in vitro from the superior oblique muscle stimulated by single and repetitive electrical pulses, applied to the trochlear nerve. Two different types of muscle fibers are described, the twitch and the slow. The slow type is characterized electrically by the presence of junctional potentials, which have reversal potentials between -10 and -20 mv, and do not show propagated responses or spikes, during nerve stimulation. When the slow muscle fibers are repetitively stimulated in situ, a prolonged contraction is maintained during stimulation. At the time, the recorded electrical activity is produced locally, at the level of the neuromuscular junctions of the slow fibers. These results indicate that the contractile mechanism of the slow muscle fibers is activated locally and segmentally.     

Effects of cortisone on mechanical activity and membrane ionic currents in frog auricular fibres.

The influence of cortisone on the mechanical and electrical activity of frog auricular fibres was investigated under voltage clamp conditions. 1. Cortisone exerted in vitro an inotropic action depending on concentration; a maximal positive inotropic effect was observed with 2 x 10(-4) g/ml of cortisone. 2. The positive inotropic effect of cortisone might be either an indirect sympathomimetic effect or an adrenaline-like effect. 3. The positive inotropic action of cortisone was correlated with modifications of the cardiac action potential: the amplitude of the action potential was enhanced while the resting membrane potential was unchanged; the amplitude and duration of the plateau were increased and the duration of the action potential was lengthened. 4. The electrical changes were related to an increase in the slow calcium current intensity resulting from an increase in the slow calcium conductance.     

Myocardial ischemia-mediated excitatory reflexes: a new function for thromboxane A2?

Clinical and experimental evidence has shown that myocardial ischemia activates cardiac spinal afferents that mediate sympathoexcitatory reflex responses. During myocardial ischemia, thromboxane A2 (TxA2) is released in large quantities by activated platelets in the coronary circulation of patients with coronary artery disease. We hypothesized that endogenous TxA2 contributes to sympathoexcitatory reflexes during myocardial ischemia through stimulation of TxA2/prostaglandin endoperoxide (TP) receptors. Regional myocardial ischemia was induced by occlusion of a diagonal branch of left anterior descending coronary artery of anesthetized cats. Hemodynamic parameters and renal sympathetic nerve activity were recorded after sinoaortic denervation and bilateral vagotomy. Regional myocardial ischemia evoked significant increases in mean blood pressure (122+/-10 vs. 139+/-12 mmHg, before vs. ischemia), aortic flow (153+/-18 vs. 167+/-20 ml/min), first derivative of left ventricular pressure at 40-mmHg developed pressure (2,736+/-252 vs. 2,926+/-281 mmHg/s), systemic vascular resistance (0.6+/-0.1 vs. 0.9+/-0.12 peripheral resistance units), and renal sympathetic nerve activity (by 22%). The reflex nature of the excitatory responses was confirmed by observing its disappearance after blockade of cardiac nerve transmission with intrapericardial 2% procaine treatment. Moreover, application of U-46619 (2.5-10 microg), a TxA2 mimetic, on the heart caused graded increases in mean arterial pressure and renal nerve activity, responses that were abolished 3 min after local blockade of cardiac neural transmission with intrapericardial procaine. BM 13,177 (30 mg/kg iv), a selective TP receptor antagonist, eliminated the reflex responses to U-46619 and significantly attenuated the excitatory responses during brief (5 min) regional myocardial ischemia. The sympathoexcitatory reflex responses to U-46619 were unchanged by blockade of histamine H1 receptors with pyrilamine and serotonin 5-HT3 receptors with tropisetron, indicating specificity of this TP receptor agonist. These data indicate that endogenous TxA2 participates in myocardial ischemia-mediated sympathoexcitatory reflex responses through a TP receptor mechanism.     

Effect of prostaglandin F2 alpha on pulmonary rapidly-adapting-receptors in the guinea pig

Pulmonary rapidly-adapting-receptors ( RARs ) are sensory nerve endings whose afferent fibers can be recorded in the vagus nerve. RARs may play a role in reflex bronchoconstriction as seen in anaphylaxis. They can be stimulated by chemical mediators of anaphylaxis, such as prostaglandin F2 alpha (PGF2 alpha). PGF2 alpha aerosol was administered to saline and bovine serum albumin (BSA)-treated guinea pigs while recording the activity of RARs . PGF2 alpha (250 micrograms/ml) given for 7-13 minutes increased both tracheal pressure and nerve activity over that produced by saline exposure in untreated guinea pigs. PGF2 alpha administered for three minutes (5-100 micrograms/ml) increased RAR nerve activity in a dose-related manner in the first five minutes of the experiment only in the BSA treated guinea pigs. Since changes in tracheal pressure did not show a significant dose-response relationship, the RARs responding to PGF2 alpha seemed to be stimulated by a direct mechanism. No correlation was shown between tracheal pressure and RAR nerve activity during PGF2 alpha treatment. Whereas, a significant correlation was found between tracheal pressure and RAR nerve activity during histamine aerosol treatment (r = 0.985). Histamine aerosol (1 to 1000 micrograms/ml, 3 min.) increased intratracheal pressure for 3 out of 4 doses. RAR nerve activity increased significantly only at the highest dose. Therefore, a possible direct effect of PGF2 alpha upon RARs exists while the effect of histamine seems dependent upon changes in airway pressure in the guinea pig.     

类α-蝎神经毒素BmKⅠ对离体大鼠心脏收缩力及电活动的特异调控

本研究探讨了一种特异性钠通道调制剂(Buthus martensi Karsch,BmKⅠ)对离体大鼠心脏收缩力及电活动的调制作用.离体心脏灌流实验显示(1)BmKⅠ(0.5-10 μmol/L)剂量依赖地增强大鼠心肌收缩力,左心室最大发展压(LVDPmax)以及dp/dtmax与对照组相比均显著增强(n=6,P＜0.05),同时可触发正性变时作用(n=6,P＜0.05);(2)大剂量BmKⅠ(20μmol/L)引起负性肌力作用及心动过缓;(3)冠脉流量随心脏收缩力的增强反而减小,应用500nmol/L BmKⅠ时冠脉流量由14.5 ml/min降至8.6 ml/min(n=6,P＜0.05);此外,心电图记录表明BmKⅠ(0.5-10μmol/L)可触发心动过速及复杂的心律失常等电活动变化;正常灌流液洗脱后BmKI引起的大鼠心脏收缩力及电活动的改变可部分恢复.由于β-肾上腺素能受体阻滞剂普奈洛尔预先应用抑制了儿茶酚胺类神经递质的释放,提示BmKⅠ引起的大鼠心脏收缩力及电活动的改变不是由于其调节儿茶酚胺类神经递质的释放及随后β-肾上腺素能受体的激活,而可能与其对心肌电压门控钠通道的调控有关.     

The role of slow potassium current in phenomena of voltage-dependent action of 4-aminopyridine in amphibian myelinated nerve fibres

The mechanism underlying the voltage-dependent action of 4-aminopyridine (4-AP) is investigated in experiments on amphibian myelinated nerve fibres (Rana ridibunda Pallas) by way of extracellular recording of electrical activity and using activators of potassium current (potassium-free solution and nitric oxide NO) and inhibitors of sodium current (tetrodotoxin). Measurement of action potential (AP) areas was used to evaluate the extent of general membrane depolarization during the activity of nerve fibres. Tetrodotoxin-induced decrease in general membrane depolarization (when the action potential amplitude was reduced by less than 20%) leads to an increase in the duration of depolarizing after-potential (DAP). This supports the dependence of time course of DAP in the presence of 4-AP on ratio of fast and slow potassium channels. In the absence of 4-AP, potassium-free solution and NO increase the potassium current through fast potassium channels (decreasing AP duration, reducing DAP and sometimes producing fast hyperpolarizing after-potential (HAP) after shortened AP), and in the presence of 4-AP these activators increase potassium current through unblocked slow potassium channels (making the development of slow HAP induced by 4-AP more rapid). The increase of slow HAP induced by 4-AP under the influence of potassium-free solution with NO supports the idea that slow HAP is due to activation of slow potassium channels and argues against the notion of removal of block of fast potassium channels. All analyzed phenomena of voltage-dependent action of 4-AP in amphibian myelinated nerve fibers can be accounted for by the activation of slow potassium current produced by membrane depolarization and a decrease of the amount of fast potassium channels involved in the membrane repolarization.     

Effect of tetrodotoxin and ethmozine on arrhythmias of a dog heart isolated in the late stage of experimental myocardial infarct

Dog hearts with ventricular extrasystole that developed 24 hours after coronary artery occlusion were isolated and perfused with blood from support dogs. After heart isolation the rhythm disturbances persisted regardless the decreased frequency of the ventricular beats. Administration of tetrodotoxin (4 X 10-8--10-7 g/ml) and ethmozine (3--5X X10-5 g/ml) abolished ventricular arrhythmias and restored the sinus rhythm. Potential mechanisms of the increased susceptibility of ischemic myocardial fibers to tetrodotoxin and antiarrhythmic drugs are discussed.     

Detection of leukotriene C4-liked immunoreactivity in tear fluid from subjects challenged with specific allergen

Tear fluid was obtained from allergic subjects from control eyes and eyes challenged with specific allergen and levels of leukotriene C4 (LTC4)-immunoreactivity determined by radioimmunoassay. Formal identification of the leukotrienes released was not possible but the levels of LTC4-immunoreactive material in allergen-challenged tear fluid (4.9 +/- 2.3 ng/ml, n = 9) were significantly higher (p less than 0.01) than those in control tear fluid (0.07 +/- 0.06 ng/ml, n = 9). These results provide evidence that leukotrienes, which account for the biological activity of slow reacting substance of anaphylaxis, may be released in allergic reactions in vivo in man.     

Connections: heart disease, cellular electrophysiology, and ion channels.

Our purpose in this article is to examine the hypothesis that both myocardial disease and ischemia can alter the electrophysiologic function of the ion channels responsible for the cellular electrical activity of the heart. Changes in the intracellular and extracellular milieus occur during ischemia and can alter the electrophysiology of several species of ionic channels and the cellular electrophysiologic activity of cardiac myocytes. Included are 1) changes in extracellular [K+] and pH and in intracellular [Na+], [Ca2+], and pH; 2) accumulation of noxious metabolic products such as lysophosphatidylcholine; and 3) depletion of intracellular ATP. Finally, ischemia or disease (e.g., hypertrophy) can alter the electrophysiology of at least two types of K+ channels, the A-like channels underlying the transient outward current and the inward rectifier, by mechanisms that apparently do not involve alteration of either the intra- or extracellular milieus. Findings suggest that the expression of cardiac A-like channel function can be altered by hypertrophy and that at least one intrinsic conductance property of the inward rectifier can be altered by ischemia. We speculate that the control of expression, function, and regulation of cardiac ion channels can be affected at the molecular level by heart disease and myocardial ischemia.     

Responses of thoracic spinal neurons to activation and desensitization of cardiac TRPV1-containing afferents in rats

The purpose of this study was to examine how upper thoracic spinal neurons responded to activation and desensitization of cardiac transient receptor potential vanilloid-1 (TRPV1)-containing afferent fibers. Extracellular potentials of single T3 spinal neurons were recorded in pentobarbital-anesthetized, paralyzed, and ventilated male rats. To activate cardiac nociceptive receptors, a catheter was placed in the pericardial sac to administer various chemicals: bradykinin (BK; 10 microg/ml, 0.2 ml), capsaicin (CAP, 10 microg/ml, 0.2 ml), or a mixture of algesic chemicals (AC; 0.2 ml) containing adenosine 10(-3) M, BK, serotonin, histamine, and PGE(2), 10(-5) M for each. Spinal neurons that responded to intrapericardial BK and/or CAP were used in this study. Results showed that 81% (35/43) of the neurons had excitatory responses to both intrapericardial BK and CAP, and the remainder responded to either BK or CAP. Intrapericardial resiniferatoxin (RTX) (0.2 microg/ml, 0.2 ml, 1 min), which desensitizes TRPV1-containing nerve endings, abolished excitatory responses to both BK (n = 8) and CAP (n = 7), and to AC (n = 5) but not to somatic stimuli. Intrapericardial capsazepine (1 mg/ml, 0.2 ml, 3 min), a specific antagonist of TRPV1, sharply attenuated excitatory responses to CAP in 5/5 neurons, but responses to BK in 5/5 neurons was maintained. Additionally, intrapericardial capsazepine had no significant effect on excitatory responses to AC in 3/3 neurons. These data indicated that intrapericardial BK-initiated spinal neuronal responses were linked to cardiac TRPV1-containing afferent fibers, but were not dependent on TRPV1. Intraspinal signaling for cardiac nociception was mediated through CAP-sensitive afferent fibers innervating the heart.     

Neonatal rat cardiac fibroblasts express three types of voltage-gated K+ channels: regulation of a transient outward current by protein kinase C

Cardiac fibroblasts regulate myocardial development via mechanical, chemical, and electrical interactions with associated cardiomyocytes. The goal of this study was to identify and characterize voltage-gated K(+) (Kv) channels in neonatal rat ventricular fibroblasts. With the use of the whole cell arrangement of the patch-clamp technique, three types of voltage-gated, outward K(+) currents were measured in the cultured fibroblasts. The majority of cells expressed a transient outward K(+) current (I(to)) that activated at potentials positive to -40 mV and partially inactivated during depolarizing voltage steps. I(to) was inhibited by the antiarrhythmic agent flecainide (100 microM) and BaCl(2) (1 mM) but was unaffected by 4-aminopyridine (4-AP; 0.5 and 1 mM). A smaller number of cells expressed one of two types of kinetically distinct, delayed-rectifier K(+) currents [I(K) fast (I(Kf)) and I(K) slow (I(Ks))] that were strongly blocked by 4-AP. Application of phorbol 12-myristate 13-acetate, to stimulate protein kinase C (PKC), inhibited I(to) but had no effect on I(Kf) and I(Ks). Immunoblot analysis revealed the presence of Kv1.4, Kv1.2, Kv1.5, and Kv2.1 alpha-subunits but not Kv4.2 or Kv1.6 alpha-subunits in the fibroblasts. Finally, pretreatment of the cells with 4-AP inhibited angiotensin II-induced intracellular Ca(2+) mobilization. Thus neonatal cardiac fibroblasts express at least three different Kv channels that may contribute to electrical/chemical signaling in these cells.     

Cardiac contractility modulation by electric currents applied during the refractory period

Inotropic effects of electric currents applied during the refractory period have been reported in cardiac muscle in vitro using voltage-clamp techniques. We investigated how electric currents modulate cardiac contractility in normal canine hearts in vivo. Six dogs were instrumented to measure regional segment length, ventricular volume (sonomicrometry), and ventricular pressure. Cardiac contractility modulating (CCM) electric currents (biphasic square pulses, amplitude +/-20 mA, total duration 30 ms) were delivered during the refractory period between pairs of electrodes placed on anterior and posterior walls. CCM significantly increased index of global contractility (E(es)) from 5.9 +/- 2.9 to 8.3 +/- 4.6 mmHg/ml with anterior CCM, from 5.3 +/- 1.8 to 8.9 +/- 4.0 mmHg/ml with posterior CCM, and from 6.1 +/- 2.6 to 11.0 +/- 7.0 mmHg/ml with combined CCM (P < 0.01, no significant change in volume axis intercept). End-systolic pressure-segment length relations showed contractility enhancement near CCM delivery sites, but not remotely. Relaxation was not influenced. CCM increased mean aortic pressure, but did not change peripheral resistance. Locally applied electrical currents enhanced global cardiac contractility via regional changes in myocardial contractility without impairing relaxation in situ.     

Platelet-activating factor: lack of direct action on guinea pig myocardium and possible transmitter release from cardiac sympathetic nerve endings at high concentrations

Microelectrode and mechanical studies were performed with isolated guinea pig myocardium (right ventricular free walls and papillary muscles) to examine the effects of platelet-activating factor (PAF) and lysophosphatidylcholine (LPC). Low concentrations of PAF (10(-8) to 10(-6) M, a range equivalent to the blood concentrations that produce marked hypotension in vivo) had no effects on action potential configuration and contractile force. High concentrations (10(-5) to 10(-4)M) of PAF and LPC per se elicited slow response action potentials with concomitant contraction (restored contraction) in the myocardium depolarized with elevated K+ (25 mM); they also augmented slow responses and restored contractions produced by a low concentration of isoproterenol (10(-8) M). Although these results suggested there was an increase in slow Ca current, the slow responses and restored contractions thus produced were greatly suppressed or abolished by the addition of a beta-adrenoceptor blocking agent, sotalol (10(-5) M), and by pretreatment with reserpine (5 mg/kg i.p., 24 h prior). In accordance with our previous conclusions, the present results suggest that direct cardiac action is not involved in the mechanisms of hypotension produced by PAF. It was also shown that high concentrations of PAF and LPC may act nonspecifically as amphiphilic compounds to induce transmitter release from sympathetic nerve endings, which may in turn augment the Ca current channels in the myocardial cell membrane.     

Tryptophan substitution of a putative D4S6 gating hinge alters slow inactivation in cardiac sodium channels

Voltage-gated Na(+) channels display rapid activation gating (opening) as well as fast and slow inactivation gating (closing) during depolarization. We substituted residue S1759 (serine), a putative D4S6 gating hinge of human cardiac hNav1.5 Na(+) channels with A (alanine), D (aspartate), K (lysine), L (leucine), P (proline), and W (tryptophan). Significant shifts in gating parameters for activation and steady-state fast inactivation were observed in A-, D-, K-, and W-substituted mutant Na(+) channels. No gating shifts occurred in the L-substituted mutant, whereas the P-substituted mutant did not yield sufficient Na(+) currents. Wild-type, A-, D-, and L-substituted mutant Na(+) channels showed little or no slow inactivation with a 10-s conditioning pulse ranging from -180 to 0 mV. Unexpectedly, W- and K-substituted mutant Na(+) channels displayed profound maximal slow inactivation around -100 mV ( approximately 85% and approximately 70%, respectively). However, slow inactivation was progressively reversed in magnitude from -70 to 0 mV. This regression was minimized in inactivation-deficient hNav1.5-S1759W/L409C/A410W Na(+) channels, indicating that the intracellular fast-inactivation gate caused such a reversal. Our data suggest that the hNav1.5-S1759 residue plays a critical role in slow inactivation. Possible mechanisms for S1759 involvement in slow inactivation and for antagonism between fast and slow inactivation are discussed.     

Cardiac function and critical swimming speed of the winter flounder (Pleuronectes americanus) at two temperatures

Using Transonic flow probes and a uniquely designed swimming flume, we directly measured cardiac parameters (Q, cardiac output; SV, stroke volume; and fH, heart rate) in winter flounder (Pleuronectes americanus) before and during critical swim speed (Ucrit) tests at 4 and 10 degrees C. Resting Q, SV and fH averaged 9.8 ml min(-1) kg(-1), 0.5 ml kg(-1) (1.0 ml g ventricle(-1)) and 21 beats min(-1) at 4 degrees C and 15.5 ml min(-1) kg(-1), 0.5 ml kg(-1) (0.95 ml g ventricle(-1)) and 34 beats min(-1) at 10 degrees C (Q10 values of 2.13, 0.91 and 2.35, for Q, SV and fH, respectively). Cardiac output, SV and fH increased by approx. 170%, 70% and 60% at both temperatures during the Ucrit test. However, cardiac parameters generally reached near maximal levels almost immediately upon swimming and remained at these levels until Ucrit (0.65 +/- 0.06 bl s(-1) at 4 degrees C and 0.73 +/ -0.07 bl s(-1) at 10 degrees C). This rapid rise in cardiac function to near maximal levels did not appear to be the result of stress alone, as Q only fell slightly when flounder were swum for 75 min at < 0.4 bl s(-1), speeds at which they appeared to swim comfortably. Our results suggest that both Q and Ucrit have been significantly overestimated in flatfishes, and that "lift-off"/slow swimming is energetically expensive. Furthermore, they show that maximum and resting stroke volume (per g of ventricle) are extremely high in the flounder as compared with other teleosts.     

Properties of calcium channels in cardiac muscle and vascular smooth muscle

The voltage-dependent slow channels in the myocardial cell membrane are the major pathway by which Ca²⁺ ions enter the cell during excitation for initiation and regulation of the force of contraction of cardiac muscle. The slow channels have some special properties, including functional dependence on metabolic energy, selective blockade by acidosis, and regulation by the intracellular cyclic nucleotide levels. Because of these special properties of the slow channels, Ca²⁺ influx into the myocardial cell can be controlled by extrinsic factors (such as autonomic nerve stimulation or circulating hormones) and by intrinsic factors (such as cellular pH or ATP level). The slow Ca²⁺ channels of the heart are regulated by cAMP in a stimulatory fashion. Elevation of cAMP produces a very rapid increase in number of slow channels available for voltage activation during excitation. The probability of a slow channel opening and the mean open time of the channel are increased. Therefore, any agent that increases the cAMP level of the myocardial cell will tend to potentiate I_si, Ca²⁺ influx, and contraction. The myocardial slow Ca²⁺ channels are also regulated by cGMP, in a manner that is opposite to that of CAMP. The effect of cGMP is presumably mediated by means of phosphorylation of a protein, as for example, a regulatory protein (inhibitory-type) associated with the slow channel. Preliminary data suggest that calmodulin also may play a role in regulation of the myocardial slow Ca²⁺ channels, possibly mediated by the Ca²⁺-calmodulin-protein kinase and phosphorylation of some regulatory-type of protein. Thus, it appears that the slow Ca²⁺ channel is a complex structure, including perhaps several associated regulatory proteins, which can be regulated by a number of extrinsic and intrinsic factors.VSM cells contain two types of Ca²⁺ channels: slow (L-type) Ca²⁺ channels and fast (T-type) Ca²⁺ channels. Although regulation of voltage-dependent Ca²⁺ slow channels of VSM cells have not been fully clarified yet, we have made some progress towards answering this question. Slow (L-type, high-threshold) Ca²⁺ channels may be modified by phosphorylation of the channel protein or an associated regulatory protein. In contrast to cardiac muscle where cAMP and cGMP have antagonistic effects on Ca²⁺ slow channel activity, in VSM, cAMP and cGMP have similar effects, namely inhibition of the Ca²⁺ slow channels. Thus, any agent that elevates cAMP or cGMP will inhibit Ca²⁺ influx, and thereby act to produce vasodilation. The Ca²⁺ slow channels require ATP for activity, with a K_0.5 of about 0.3 mM. C-kinase may stimulate the Ca²⁺ slow channels by phosphorylation. G-protein may have a direct action on the Ca²⁺ channels, and may mediate the effects of activation of some receptors. These mechanisms of Ca²⁺ channel regulation may be invoked during exposure to agonists or drugs, which change second messenger levels, thereby controlling vascular tone.     

Factors determining the duration of a single postsynaptic response in neuromuscular junctions

Parameters of single acetylcholine-activated ionic channels and the time course of miniature end-plate currents (MEPC) were compared in experiments on fast and slow lamprey, frog, chicken, and rat muscle fibers. The mean open time of the channels was shown to be the principal, but not the only factor determining the duration of MEPC. The role of the remaining factors and, in particular, of insufficiency of acetylcholinesterase activity, in slow muscle fibers and also in "giant" MEPC generation, is much greater than in fast fibers or during ordinary MEPC generation. Relatively low acetylcholinesterase activity favors asynchronous interaction between acetylcholine molecules and receptors, which delays the time course of synaptic responses. Mechanisms of acceleration of MEPC decay under the influence of -bungarotoxin and D-tubocurarine, and also the conditions for MEPC generation in different regions of the neuromuscular junction are discussed.I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 16, No. 5, pp. 590–602, September–October, 1984.     

Motor pattern generation of the posterior cardiac plate-pyloric system in the stomatogastric ganglion of the mantis shrimp Squilla oratoria

Activity patterns of the constituent neurons of the posterior cardiac plate-pyloric system in the stomatogastric ganglion of the mantis shrimp Squilla oratoria were studied by recording spontaneous burst discharges intracellularly from neuronal somata. These neurons were identified electrophysiologically, and synaptic connections among them were qualitatively analysed. The posterior cardiac plate constrictor, pyloric constrictor, pyloric dilator and ventricular dilator motoneurons, and the pyloric interneuron were involved in the posterior cardiac plate-pyloric system. All the cell types could produce slow burst-forming potentials which led to repetitive spike discharges. These neurons generated sequentially patterned outputs. Most commonly, the posterior cardiac plate neuron activity was followed by the activity of pyloric constrictor neurons, and then by the activity of pyloric dilator/pyloric interneuron, and ventricular dilator neurons. The motoneurons and interneuron in the posterior cardiac plate-pyloric system were connected to each other either by electrical or by inhibitory chemical synapses, and thus constructed the neural circuit characterized by a wiring diagram which was structurally similar to the pyloric circuit of decapods. The circuitry in the stomatogastric ganglion was strongly conserved during evolution between stomatopods and decapods, despite significant changes in the peripheral structure of the foregut. There were more electrical synapses in stomatopods, and more reciprocal inhibitory synapses in decapods.Abbreviations EJP excitatory junctional potential - IPSP inhibitory postsynaptic potential - CoG commissural ganglion - CPG central pattern generator - ion inferior oesophageal nerve - OG oesophageal ganglion - pcp posterior cardiac plate - son superior oesophageal nerve - STG stomatogastric ganglion - stn stomatogastric nerve - PY pyloric constrictor - PD pyloric dilator - VD ventricular dilator - AB pyloric interneuron - lvn lateral ventricular nerves - tcpm transverse cardiac plate muscle