Decubitus CT Myelography for CSF-Venous Fistulas: A Procedural Approach.

Decubitus CT myelography is a reported method to identify CSF-venous fistulas in patients with spontaneous intracranial hypotension. One of the main advantages of decubitus CT myelography in detecting CSF-venous fistulas is using gravity to dependently opacify the CSF-venous fistula, which can be missed on traditional myelographic techniques. Most of the CSF-venous fistulas in the literature have been identified in patients receiving general anesthesia and digital subtraction myelography, a technique that is not performed at all institutions. In this article, we discuss the decubitus CT myelography technique and how to implement it in daily practice.

Hyperpolarization and lysophosphatidylcholine induce inward currents and ethidium fluorescence in rabbit ventricular myocytes.

Strong electric pulses produce reversible or irreversible membrane breakdown (electroporation). We analysed the permeation properties of minute pores caused by hyperpolarization or lysophosphatidylcholine (LPC) by comparing the amount of charge carried by irregular inward currents (I(hi)) with changes in ethidium bromide (EB) fluorescence in isolated rabbit ventricular myocytes. Forty-second negative pulses from a holding potential of -20 mV induced I(hi) whose conductance increased with hyperpolarization; the mean conductance (G(hi)) was 63.6 +/- 9.9 pS pF(-1) (mean +/- S.E.M., n = 9) at -160 mV. EB fluorescence increased during voltage pulses in parallel with the time integral of I(hi) (Q(hi)), with the magnitude of the increases in nuclear EB fluorescence being 5.3 times greater than in the cytoplasm at -160 mV. Similar hyperpolarization-induced parallel increases in I(hi) and EB fluorescence were also obtained in Na(+)-free, N-methyl-D-glucamine (NMDG) solution. LPC (10 microM) induced large (101.2 +/- 21.2 pS pF(-1), n = 16), rapid (rise times, 1-10 ms) I(hi) with slow relaxation rates at -80 mV that reflected increases in G(hi) to 94.3 +/- 24.8 pS pF(-1) (n = 8) at 6 min. Plots of EB fluorescence vs. Q(hi) were well fitted by a common Hill's equation with a Hill coefficient of 0.97. Taken together, our findings indicate that hyperpolarization and LPC produced pores having the same filter properties for the permeation of small ions, including ethidium(+), and that I(hi) (carried in part by Ca(2+)) generated by membrane breakdown are capable of supplying sufficient ions to evoke abnormal excitation and contraction in cardiac myocytes.

Properties of voltage-gated Ca(2+) channels in rabbit ventricular myocytes expressing Ca(2+) channel alpha(1E) cDNA.

Using the whole-cell patch-clamp technique, we have studied the properties of alpha(1E) Ca(2+) channel transfected in cardiac myocytes. We have also investigated the effect of foreign gene expression on the intrinsic L-type current (I(Ca,L)). Expression of green fluorescent protein significantly decreased the I(Ca,L). By contrast, expression of alpha(1E) with beta(2b) and alpha(2)/delta significantly increased the total Ca(2+) current, and in these cells a Ca(2+) antagonist, PN-200-110 (PN), only partially blocked the current. The remaining PN-resistant current was abolished by the application of a low concentration of Ni(2+) and was little affected by changing the charge carrier from Ca(2+) to Ba(2+) or by beta-adrenergic stimulation. On the basis of its voltage range for activation, this channel was classified as a high-voltage activated channel. Thus the expression of alpha(1E) did not generate T-like current in cardiac myocytes. On the other hand, expression of alpha(1E) decreased I(Ca,L) and slowed the I(Ca,L) inactivation. This inactivation slowing was attenuated by the beta(2b) coexpression, suggesting that the alpha(1E) may slow the inactivation of I(Ca,L) by scrambling with alpha(1C) for intrinsic auxiliary beta.

Independent modulation of L-type Ca2+ channel in guinea pig ventricular cells by nitrendipine and isoproterenol.

Dihydropyridine (DHP) Ca2+ channel blockers decrease L-type Ca2+ channel current (I(CaL)) by enhancing steady-state inactivation, whereas beta-adrenergic stimulation increases I(CaL) with small changes in the kinetics. We studied the effects of DHP Ca2+ channel blockers on cardiac I(CaL) augmented by beta-adrenergic stimulation. We recorded I(CaL) as Ba2+ currents (I(Ba)) from guinea pig ventricular myocytes using the whole-cell patch clamp technique. and compared the effects of nitrendipine (NIT) in the absence and presence of isoproterenol (1 microM, ISO) or forskolin (10 microM, FSK). Maximal I(Ba) elicited from a holding potential of -80 mV were diminished to 69.4+/-13.5% (mean and SE, n=5) of control by NIT (100 nM) and the diminished I(Ba) were increased to 180.3+/-23.2% of control by ISO in the presence of NIT, which was similar to the enhancement seen in the absence of NIT. NIT shifted the V(1/2) of the I(Ba) inactivation curve from -34.6+/-1.9 mV (n=5) to -48.7+/-1.2 mV, enhancing I(Ba) decay with shortening T(1/2) at -10 mV from 164.6+/-24.2 ms (n=7) to 105.4+/-15.2 ms. ISO elicited a small additional shift in the V(1/2) of I(Ba) inactivation in the same direction. ISO and FSK each slowed I(Ba) decay in the absence of NIT, but not in its presence. Thus, beta-adrenergic agonists increase and DHP Ca2+ channel blockers decrease the amplitude of cardiac I(CaL) independently and the kinetics of I(CaL) is determined mainly by the latter when these drugs coexist.

Activation of TxA2/PGH2 receptors and protein kinase C contribute to coronary dysfunction in superoxide treated rat hearts.

We have previously shown that superoxide anion (O2-) stimulates the release of vasoconstrictor prostanoids and induces a prolonged rise in coronary perfusion pressure (CPP) that persists even after removal of O2-. In this study, we tested the hypothesis that the increased CPP is mediated by activation of TxA2/ PGH2 (TP) receptors and protein kinase C (PKC)-dependent mechanisms. In Langendorff perfused rat hearts, O2- was applied for 15 min and then washed out over a period of 20 min. Application of O2- increased the release of vasoconstrictive (TxA2 and PGF2alpha) and decreased vasodilating (PGI2 and PGE2) prostanoids. Although indomethacin (10 microM), a cyclooxygenase inhibitor, attenuated the rise in CPP during O2- perfusion, the increase was not completely blocked. OKY 046Na (10 microM), a thromboxane synthase inhibitor, had no effect on O2--induced increases in CPP, whereas ONO 3708 (10 microM), a TP receptor antagonist, suppressed this effect. PKC activity was also elevated by more than 50% by O2- perfusion. CPP typically increased throughout the O2- wash-out. This post-O2- vasoconstriction was not inhibited by indomethacin, nitroglycerin or nitrendipine. In contrast, ONO 3708 (10 microM) and two PKC inhibitors, staurosporine (10 nM) and calphostin C (100 nM), completely blocked the rise in CPP, and even elicited vasodilation. PDBu enhanced the post-O2- vasoconstriction. We conclude that O2--induced coronary vasoconstriction is initially mediated by TP receptors, but activation of PKC sustains the response.

Involvement of K(+) channels in the relaxant effects of YC-1 in vascular smooth muscle.

This study addresses the question whether K(+) channels are involved in the vasorelaxant effects of 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl-indazole (YC-1 ). In rat aorta, guinea pig aorta, and guinea pig a. carotis, YC-1 inhibited contractions induced by phenylephrine (3 microM) more potently than those induced by K(+)(48 mM). In rat aorta, tetraethylammonium (10 mM), charybdotoxin (0.2 microM), and iberiotoxin (0.1 microM), but not glibenclamide (10 microM), attenuated the relaxant effects of YC-1. In guinea pig a. carotis, YC-1 (30 microM) induced a hyperpolarisation which was antagonised by 1H-[1,2,4]oxadiazolo[4, 3-a]quinoxalin-1-one (ODQ; 50 microM). In rat aorta, YC-1 (30 microM) increased the rate constant of 86Rb-efflux. The effect of YC-1 was potentiated by zaprinast (10 microM), but inhibited by ODQ (50 microM) or charybdotoxin (0.2 microM). In smooth muscle cells from rat aorta, YC-1 (10 microM) increased BK(Ca) channel activity. It is suggested that YC-1-induced vasorelaxation is partially mediated by the activation of K(+) channels.

Properties and expression of Ca2+-activated K+ channels in H9c2 cells derived from rat ventricle.

H9c2 is a clonal myogenic cell line derived from embryonic rat ventricle that can serve as a surrogate for cardiac or skeletal muscle in vitro. Using whole cell clamp with H9c2 myotubes, we observed that depolarizing pulses activated slow outward K+ currents and then slow tail currents. The K+ currents were abolished in a Ca2+-free external solution, indicating that they were Ca2+-activated K+ currents. They were blocked by apamin, a small-conductance Ca2+-activated K+ (SK) channel antagonist (IC50 = 6.2 nM), and by d-tubocurarine (IC50 = 49.4 microM). Activation of SK channels exhibited a bell-shaped voltage dependence that paralleled the current-voltage relation for L-type Ca2+ currents (ICa,L). ICa,L exhibited a slow time course similar to skeletal ICa, L, were unaffected by apamin, and were only slightly depressed by d-tubocurarine. RT-PCR analysis of the mRNAs revealed that rSK3, but not rSK1 or rSK2, was expressed in H9c2 myotubes but not in myoblasts. These results suggest that rSK3 channels are expressed in H9c2 myotubes and are primarily activated by ICa,L directly or indirectly via Ca2+-induced Ca2+ release from sarcoplasmic reticulum.

Activated stellate (Ito) cells possess voltage-activated calcium current.

We previously reported stellate (Ito) cells possess voltage-activated Ca2+ current. The activation of stellate cells has been indicated to contribute to liver fibrosis and the regulation of hepatic hemodynamics. The aim of this study was to investigate the relationship between voltage-activated Ca2+ current and activation of stellate cells. Voltage-activated Ca2+ current in stellate cells isolated from rats were studied using whole-cell patch clamp technique. L-type voltage-activated Ca2+ current was hardly detected in stellate cells cultured for less than 9 days. Ca2+ current was detected 12.5 and 69% of cells at the 10th and 14th day of culture, respectively. BrdU incorporation indicated cell proliferation was recognized over 50% of cells at the 3rd and 5th day of culture, respectively, then decreased significantly in a time-dependent manner. On the other hand, the expression of alpha-smooth muscle actin indicated cell activation increased from 7th day of culture and collagen type I mRNA appeared remarkably in cells cultured for more than 10 days. In this study, we concluded L-type voltage-activated Ca2+ current was recognized in activated stellate (myofibroblast-like) cells.

Low K+-induced hyperpolarizations trigger transient depolarizations and action potentials in rabbit ventricular myocytes.

1. The effects of large reductions of [K+]o on membrane potential were studied in isolated rabbit ventricular myocytes using the whole-cell patch clamp technique. 2. Decreasing [K+]o from the normal level of 5.4 mM to 0.1 mM increased resting membrane potential (Vrest) from -75.6 +/- 0.3 to -140.3 +/- 1.9 mV (means +/- s.e.m; n = 127), induced irregular, transient depolarizations with mean maximal amplitudes of 19.5 +/- 1.5 mV and elicited action potentials in 56.7 % of trials. The action potentials exhibited overshoots of 37.9 +/- 1.5 mV (n = 72) and sustained plateaux. 3. Addition of 0.1 mM La3+ in the presence of 0.1 mM [K+]o significantly increased Vrest but decreased the amplitude of transient depolarizations and suppressed the firing of action potentials. 4. Replacement of external Na+ or Cl- with N-methyl-D-glucamine or aspartate, respectively, or internal dialysis with 10 mM EGTA or BAPTA had little effect on low [K+]o-induced membrane potential changes. 5. Hyperpolarizing voltage clamp pulses to potentials between -110 and -200 mV activated irregular inward currents that increased in amplitude and frequency with increasing hyperpolarization and were depressed by 0.1 mM La3+. 6. The generation of transient depolarizations by low [K+]o can be explained as being a consequence of decreasing the inward rectifier K+ current (IK1) and the appearance of inward currents reflecting electroporation resulting from strong electric fields across the membrane.

Alcohol stimulates the expression of L-type voltage-operated Ca2+ channels in hepatic stellate cells.

Hepatic stellate cells (HSCs) have L-type voltage-operated Ca2+ channels (VOCC). However, the effect of ethanol on VOCC is unknown. To investigate the mechanism of ethanol-induced liver injury, the effect of ethanol on VOCC in HSCs was studied. In control cells, VOCC revealed by patch clamp techniques were not detected in cells cultured for less than 7 days; however, a faint VOCC mRNA by reverse-transcription polymerase chain reaction was recognized at the 5(th) day of culture. Detection of VOCC increased from 8% on day 7 to over 50% on day 14 in controls. With ethanol (100mM), it increased from 12% on day 5 to 100 % on day 14. Furthermore, expression of alpha-smooth muscle actin, shown as transformation to a myofibroblast, was recognized in ethanol-treated cells earlier and stronger than that in controls. VOCC were up-regulated by the treatment with ethanol associated with the induction of transformation to myofibroblasts.

CT angiography of cerebral vasospasm with conventional angiographic comparison.

Two patients with subarachnoid hemorrhage underwent CT angiography and conventional angiography at presentation. In each patient, both studies were repeated after the onset of intracranial vasospasm. In both cases, CT angiograms were able to demonstrate convincingly the conventional angiographic findings. CT angiography may prove useful in the evaluation of vasospasm in patients with subarachnoid hemorrhage.

Superoxide and nitroglycerin stimulate release of PGF2 alpha and TxA2 in isolated rat heart.

The aim of this study was to investigate the effects of nitroglycerin (NTG), a nitric oxide (NO) donor used as a vasodilating agent, on prostanoid [e.g., prostaglandin (PG)] release in the O2(-)-pretreated rat heart. Perfusion of O2-, generated by a xanthine oxidase-purine coupling, caused elevation (P < 0.05) of the coronary perfusion pressure (CPP) after 20 min (from 57.1 +/- 3.9 during the control period to 72.2 +/- 3.9 mmHg, P < 0.05). O2- caused increased release of PGF2 alpha from 3.6 +/- 0.7 to 20.6 +/- 4.4 pmol.min-1.g-1 and of thromboxane A2 (TxA2) from 2.4 +/- 0.4 to 9.6 +/- 1.6 pmol.min-1.g-1 (P < 0.001) with no significant changes in PGE2 and PGI2 release. During the 20-min washout of O2- from the heart with normal Krebs solution, release of PGF2 alpha and TxA2 decreased to 8.7 +/- 1.4 and 6.3 +/- 1.7 pmol.min-1.g-1, respectively, and the release of PGE2 and PGI2 markedly increased from 11.1 +/- 2.9 to 25.4 +/- 3.6 and 157.2 +/- 16.4 to 413.2 +/- 41.4 pmol.min-1.g-1, respectively (P < 0.05), without lowering the elevated CPP. Administration of 4 microM NTG during the washout period paradoxically augmented the elevated CPP to 133.3 +/- 0.6% and was associated with a doubling (P < 0.05) of PGF2 alpha and TxA2 release with no significant changes in PGE2 and PGI2 release. The NTG-induced CPP elevation was inhibited (P < 0.05) by indomethacin, a cyclooxygenase inhibitor, or ONO-3708, a TxA2 receptor blocker, whereas arachidonic acid, a substrate for PG synthesis, augmented the CPP elevation. These results indicate that NTG stimulates the synthesis of vasoconstrictive PG in the O2(-)-pretreated rat heart, inducing a paradoxical elevation in CPP.

Decrease in Ca2+ sensitivity as a mechanism of hydrogen peroxide-induced relaxation of rabbit aorta.

OBJECTIVE: In vascular strips, hydrogen peroxide (H2O2) relaxes alpha 1-adrenergic agonist-induced but not high-K(+)-induced contractions. The aim of this study was to explore H2O2-induced changes in [Ca2+]i of vascular smooth muscle and to elucidate the mechanisms of action of H2O2. METHODS: Isolated rabbit aortic strips were isometrically contracted with high-K+ (64.7 mM) or phenylephrine (PE, 0.3 microM). The effects of 300 microM H2O2 on [Ca2+]i of endothelium-denuded vascular smooth muscle and tension were determined simultaneously by the fura-2 method. Changes in [Ca2+]i were expressed as percentages of high-K(+)-induced values measured at the beginning of the experiments. In another series of experiments, the relaxant effect of 300 microM H2O2 was examined in high-K+ (20 mM)-induced contraction in the presence of the protein kinase C activator, phorbol 12,13-dibutyrate (PDBu). RESULTS: Hydrogen peroxide caused a reversible rise in [Ca2+]i of vascular smooth muscle under both resting conditions and in the precontracted state. During high-K(+)-induced contraction, H2O2 further increased [Ca2+]i by 26.6(s.e.m. 1.7)% accompanied by a small increase in tension of 6.5(1.9)% of high-K(+)-induced tension. By contrast, during PE-induced contraction, although H2O2 caused a comparable additional increase in [Ca2+]i (26.4(4.7)%), muscle tension fell by 28.9(2.2)% of the steady-state PE-induced tension. Hydrogen peroxide had a relaxant effect on augmented high-K(+)-induced contraction in which Ca2+ sensitivity of the contractile apparatus was elevated by PDBu. CONCLUSIONS: In spite of its effect of increasing [Ca2+]i of vascular smooth muscle, hydrogen peroxide causes relaxation of endothelium-denuded, PE-precontracted rabbit aorta. The mechanism is probably through suppression of agonist-induced augmentation of Ca2+ sensitivity of the contractile apparatus.

The tetravalent organic cation spermine causes the gating of the IRK1 channel expressed in murine fibroblast cells.

1. The activation kinetics of the IRK1 channel stably expressed in L cells (a murine fibroblast cell line) were studied under the whole-cell voltage clamp. Without polyamines or Mg2+ in the pipettes, inward currents showed an exponential activation on hyperpolarization. The steep inward rectification of the currents around the reversal potential (Erev) could be described by the open-close transition of the channel with first-order kinetics. 2. When the tetravalent organic cation spermine (Spm) was added in the pipettes, the activation kinetics changed; this was explicable by the increase in the closing rate constant. The activation of the currents observed without Spm or Mg2+ in the pipettes was ascribed to the unblocking of the 'endogenous-Spm block'. 3. In the presence of the divalent cation putrescine (Put) or of Mg2+ in the pipettes, a different non-conductive state suppressed the outward currents on depolarization; the channels instantaneously changed to the open state on repolarization. As the depolarization was prolonged, this non-conductive state was replaced by the non-conductive state that shows an exponential activation on repolarization. This phenomenon was attributed to the redistribution of the channels from the Put- or Mg(2+)-blocked state to the 'endogenous Spm-blocked state' during depolarization. 4. In the presence of the trivalent cation spermidine (Spd) in the pipettes, two different non-conductive states occurred, showing a faster and a slower activation on repolarization. The rectification around Erev was mainly due to the non-conductive state showing a faster activation, which appeared to be the Spd-blocked state. During depolarization, redistribution of the channels to the 'endogenous Spm-blocked state' also occurred. 5. In the presence of Spd, Put or Mg2+ in the pipettes, the voltage dependence of the activation time constant reflecting the unblocking of the 'endogenous Spm' was shifted in the hyperpolarizing direction. 6. Our results suggest that the 'intrinsic gating' that shows the time-dependent activation on repolarization, and that is responsible for the inward rectification around Erev, reflects the blocking kinetics of the tetravalent Spm.

Depression of ATP-induced Ca2+ signalling by high K+ and low Cl- media in human aortic endothelial cells.

We studied the contribution of the Cl- channel as well as K+ channel in the regulation of Ca2+ signalling in fura-2-loaded cultured human aortic endothelial cells. Low Cl- (20 mM) superfusion did not affect the ATP (10 microM)-induced [Ca2+]i increase at the initial peak (control 309 +/- 30 nM (mean +/- SD, n = 17) versus 20 mM [Cl-]o 308 +/- 40 nM (n = 8)) but depressed it at the sustained phase (at 5 min, 170 +/- 29 nM versus 85 +/- 10 nM). Similar selective depression of the sustained phase occurred also in Ca(2+)-free and 140 mM K+ solutions and in the presence of niflumic acid (300 microM), a blocker of the Cl- channel and Ca2+ permeable cation channel. After application of ATP, the increase of [Cl-]o from 20 to 146 mM resulted in a Ca2+ overshoot. Both Cl- and K+ channels play an important role in the regulation of Ca2+ influx presumably by controlling the membrane potential in vascular endothelial cells.

Inhibition of vasoactive amine induced contractions of vascular smooth muscle by hydrogen peroxide in rabbit aorta.

OBJECTIVE: The aims were to investigate the effects of H2O2 on arterial contractions induced by vasoactive amine agonists and a high concentration of potassium ions (high K+) in vitro and to explore the possible underlying mechanism(s) involved. METHODS: Isometric tension of rabbit isolated aortic strips was measured and the effects of pretreatment with H2O2 on contractions induced by phenylephrine and high K+ were compared. The effects of H2O2 on precontracted strips were determined in the presence and absence of the aortic endothelium and compared with those of acetylcholine. RESULTS: The tension developed in response to an agonist was expressed as a percentage of the contraction induced by high K+ (64.7 mM) superfusion. Pretreatment with 300 microM H2O2 reduced the mean phenylephrine (0.3 microM) induced contraction from 96.2(SEM 1.4) to 61.8(2.8)%; the effect was stable and reversed by washing out the H2O2. Hydrogen peroxide relaxed phenylphrine precontracted strips with and without endothelium but it showed no relaxant effect when the strips were precontracted by high K+, whereas acetylcholine (1 microM) induced transient relaxation of high K+ precontracted strips by 27.8(2.9)%. The relaxant effect of H2O2 was not affected by pretreatment with indomethacin (a cyclo-oxygenase inhibitor), desferrioxamine (a hydroxyl radical scavenger), or diphenylphenylenediamine (a lipophilic antioxidant). CONCLUSIONS: H2O2 inhibits vasoactive amine induced contractions of the vascular smooth muscle of rabbit aorta in vitro without affecting voltage dependent Ca2+ influx or contractile machinery. The mechanism responsible for its inhibitory effects may be related to impairments of the cellular signalling reactions initiated by the agonists.

Indirect activation by internal calcium of chloride channels in endothelial cells.

The action of internal Ca2+ on Cl- channels in endothelial cells was studied by the whole-cell clamp technique in cultured human aortic endothelial cells. Intracellular Ca2+ application by break-in of a Ca(2+)-containing pipette solution produced an outward-rectifying Cl- current after a few minutes delay. The amplitude of the Cl- current increased with the increase in the internal Ca2+ concentration, producing a maximal Cl- conductance as large as 2 nS/pF at pCa 5. The increase of the Ca(2+)-induced Cl- conductance was also dependent on the internal ATP concentration. At pCa 5, the Cl conductance per cell was 61 nS at 5 mM ATP and 24 nS at 1 mM. The calmodulin antagonists trifluoperazine and W-7 blocked the Cl- channel reversibly. The results suggest that Ca2+ activates the Cl- channels indirectly via a calmodulin-mediated pathway, and that binding of ATP to the channel is a prerequisite for activation.

ATP-induced chloride current and tonic increase of internal Ca2+ concentration in vascular endothelial cells.

The effect of ATP on membrane currents and the intracellular Ca2+ concentration was investigated in cultured human aortic endothelial cells. ATP (10 microM) activated the Cl- current within a few minutes following a rapid activation of the K+ current. Fura-2 fluorometry showed that ATP increased [Ca2+]i with a biphasic time course. The tonic phase was markedly depressed by both an increase in [K+]o to 140 mM and a decrease in [Cl-]o to 20 mM. ATP activated not only Ca(2+)-activated K+ channels but also Cl- channels to regulate the membrane potential related to the tonic phase of the [Ca2+]i increase.

L-type calcium channel activity in human atrial myocytes as influenced by 5-HT.

5-Hydroxytryptamine (10 mumol/l; 5-HT) exerted a positive inotropic effect associated with an increase in the Ca2+ current (ICa) in the human right atrium. For detailed analysis, L-type Ca2+ channel currents were recorded from cell-attached patches using 100 mmol/l Ba2+ as charge carrier. Ca2+ channel activity was identified, first, by burst-like inwardly directed currents and, second, by the appearance of long channel openings promoted by Bay K 8644 (1 mumol/l) upon repetitive depolarizations from -80 to 0 mV. The unitary conductance of the Ca2+ channel amounted to 25.8 pS. During superfusion with 5-HT, ensemble averaged (mean) current was enhanced by about 60%. The increase in mean current was brought about by an increase in the channel availability, defined as the ratio of sweeps containing Ca2+ channel activity to the total number of depolarizations. The open probability of a single Ca2+ channel within a sweep with channel activity, unitary conductance, mean open and mean shut times of the channel, however, remained unaffected during superfusion with 5-HT (n = 10). The 5-HT-induced increase in macroscopic ICa in the human atrium can therefore be explained by an enhanced availability of Ca2+ channels to open upon depolarization. The observed changes in gating properties of the human Ca2+ channel by 5-HT are very similar to those which are known from isoprenaline-induced cAMP-dependent phosphorylation of the Ca2+ channel protein in other tissues.

[Recent progress of research on cardiac ion channels].

The paper summarizes the recent progress of research on the structure, function and regulation of cardiac ion channels. The primary structures of voltage-gated Na and Ca channels are homologous, with identical voltage sensors and homologous pore structure. The voltage-gated channels are modulated by sympathetic and vagal transmitters. beta-Stimulants phosphorylate various channels by activating cyclic AMP-dependent kinase, while acetylcholine antagonizes this phosphorylation. The phosphorylation inhibits the Na current by promoting inactivation, increases the L-type Ca current by increasing the channel availability, increases the delayed rectifying K current and induces Cl current. Acetylcholine induces a K current in nodal and atrial cells via a direct binding of beta gamma subunit of GTP-binding protein (GK) to the K channel.