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H Reuter

Publications and source records attributed to H Reuter.

At least 91 records · Page 5Linked to original sources
PubMed1987

Calcium channel modulation by beta-adrenergic neurotransmitters in the heart.

Calcium ions play a crucial role in the regulation of the heart beat. During each action potential Ca2+ ions flow into the cell and are directly and indirectly involved in generation of pacemaker potentials and of contractile force. Adrenergic and cholinergic neurotransmitters modulate Ca2+ influx. The most detailed analysis has been made on the mechanism of the beta-adrenergic effect on calcium channels in cardiac cell membranes. This is briefly summarized in a personal account, while for more detailed information the reader is referred to more extensive recent reviews.

Adrenergic beta-Agonists↗
PubMed1987

Voltage-dependent cooperative interactions of calcium channel ligands in intact cardiac cells.

Voltage-dependent Ca channels were studied in living, tissue cultured rat heart cells using patch clamp analysis of single channels and radioligand binding studies at different membrane potentials. Ca channel activating and blocking dihydropyridines (DHP) show cooperative interaction and, therefore, bind to at least two different binding sites on the channel protein. Cooperative interactions between activating and blocking DHP, between DHP and verapamil and between DHP and diltiazem are all voltage dependent. The type of interaction in polarized cells and hence, the possible effects in vivo cannot be predicted from studies in cell homogenates.

Allosteric Site↗
PubMed1986

Voltage-dependent mechanisms for raising intracellular free calcium concentration: calcium channels.

Single-channel recording by means of the patch-clamp technique provides a method for observing the kinetic properties of individual ion channels. Three distinct types of voltage-dependent calcium channels have so far been characterized: T-type channels are responsible for a rapidly inactivating, transient Ca2+ current; L-type channel openings produce a long-lasting Ca2+ current. N-type channels have the kinetic features of neither T- nor L-type channels. In addition to differences in their gating and conductance properties the three types of channels can also be distinguished by their different sensitivities to pharmacological intervention. The respective distribution of the various types of Ca2+ channels may vary from tissue to tissue. For example, more L-type Ca2+ channels may open during excitation in cardiac and smooth muscle cells than in nerve cells, where the other channel types may prevail. This would explain the different sensitivities of these tissues to dihydropyridines. In view of their functional significance it will be of considerable interest to explore in greater detail the respective densities and sensitivities to neurotransmitters and drugs of various Ca2+ channels in different tissues.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1986

Properties and modulation of cardiac calcium channels.

Voltage-dependent calcium channels are widely distributed in excitable membranes and are involved in the regulation of many cellular functions. These channels can be modulated by neurotransmitters and drugs. There is one particular type of calcium channel in cardiac cells (L-type) whose gating is affected in different ways by beta-adrenoceptor and 1,4-dihydropyridine agonists. We have analysed single calcium channel currents (i) in myocytes from rat hearts in the absence and presence of isoproterenol or 8-bromo-cAMP. We have found that both compounds have similar effects on calcium channel properties. They increase the overall open state probability (po) of individual calcium channels while i remains unaffected. Analysis of the gating kinetics of calcium channels showed: a slight increase in the mean open times of calcium channels, a reduction in time intervals between bursts of channel openings, an increase in burst length and a prominent reduction in failures of calcium channels to open upon depolarization. These kinetic changes caused by isoproterenol and 8-bromo-cAMP can account for the increase in po. Since the macroscopic calcium current, ICa, can be described by ICa = N X po X i, the increase in po accounts for the well-known increase in ICa by beta-adrenergic catecholamines. Cyclic AMP-dependent phosphorylation of calcium channels is a likely metabolic step involved in this modulation. Another class of drug that modulates calcium channel gating is the 1,4-dihydropyridines which can either enhance or reduce ICa, either by prolonging the open state of the channels or by facilitating the inactivated state. Both effects depend strongly on membrane potential and are independent of cyclic AMP-dependent phosphorylation reactions.

Adrenergic beta-Agonists↗
PubMed1986

Studies on Ca channels in intact cardiac cells: voltage-dependent effects and cooperative interactions of dihydropyridine enantiomers.

We have investigated the effects of two oppositely acting enantiomers of the 1,4-dihydropyridine derivative 202-791 on voltage-dependent Ca channels by combining electrophysiological techniques and binding studies. The (S)-enantiomer of 202-791 promoting prolonged openings of single Ca channels, and thereby increasing transmembrane Ba currents, was classified as channel activator. The (R)-enantiomer favoring a closed state of the channel, and thereby reducing Ba currents, was classified as a channel blocker. Both compounds shifted the steady state current inactivation curve toward more negative potentials. At holding potentials positive to -20 mV, the Ca channel-activating effect of the (S)-enantiomer turned over into a blocking effect. In cells with normal resting potential the combination of the two enantiomers revealed a possible positive cooperative effect resulting in an enhancement of the open state probability of the channels. At depolarized holding potentials the activator enhanced the inhibitory effect of the blocker. Binding studies in intact cells were performed by using the radiolabeled channel-blocking dihydropyridine 3H-(+)-PN 200-110. The results showed a strong increase in binding affinity but no change in binding capacity when the cells were depolarized. Analysis of the interactions of (S)- and (R)-202-791 with this radioligand indicated stimulation of 3H-(+)-PN 200-110 binding by the (S)-enantiomer in polarized cells (membrane potential -38 +/- 4 mV). This effect could be attributed to an increase in binding affinity. The (R)-enantiomer had no such positive cooperative effect, but acted as a purely competitive ligand. Depolarization to 0 mV increased the apparent affinity of both enantiomers by factors of 38 (blocker) and 12 (activator), but abolished the cooperative effect of (S)-202-791 on the binding of the radioligand. Ca ions had little effect on the binding of 3H-(+)-PN 200-110 in polarized cells. However, in the presence of the activating (S)-enantiomer, Ca transformed the usual hyperbolic binding isotherm of the radioligand into a strongly sigmoid curve. Sigmoidicity was minimal with 3-5 microM Ca and maximal with 0.5 mM Ca. Together these data demonstrate homotropic and heterotropic cooperative interactions between channel activator and channel blocker. They indicate that at least two high affinity binding sites for dihydropyridines are associated with voltage-dependent Ca channels. Voltage dependence of both--binding affinity and cooperativity--suggests that these binding sites are located close to a structural component of the channel which is involved in the potential-sensitive gating process.

Aging↗
PubMed1986

The voltage-dependent effect of 1,4-dihydropyridine enantiomers on Ca channels in cardiac cells.

We studied voltage-dependent binding and action of 1,4-dihydropyridine enantiomers (Sandoz (+)-(S) & (-)-(R)-202-791) in intact cardiac cells. Drug action was studied by patch clamp method. (+)-enantiomer primarily prolonged open time of Ca channel, thus enhancing Ca currents, while (-)-enantiomer predominantly favored closed state of the channel, reducing the currents. Electrophysiological study also revealed that steady-state inactivation was greatly enhanced by both enantiomers. Therefore, it seems that both enantiomers have a capability of activating and blocking effects. Strongly voltage-dependent binding affinity of these enantiomers was revealed by displacement of 3H-(+)-PN200-110 with each enantiomers. Binding affinity of both enantiomers in depolarized cells was much higher than in polarized cells. These results indicate that both enantiomers have higher affinity when Ca channels are inactivated.

Animals↗
PubMed1985

Regulation by 8-Br-cAMP of beta-adrenoceptors in cultured myocardial cells.

Primary cultures of myocardial cells from neonatal rats were exposed for up to 5 days to the cyclic AMP derivative 8-Br-cAMP. After one day of exposure to the nucleotide, an increase in specific binding capacity of the hydrophilic beta-adrenoceptor antagonist 3H-CGP 12177 was observed in intact cells. (-)-Isoprenaline displaced the radioligand from its binding site. Neither the KD of the antagonist, nor that of the agonist were significantly affected by 8-Br-cAMP. The loss of beta-adrenoceptors during desensitization by long term treatment of the cells with isoprenaline could be partially prevented by 8-Br-cAMP. Only in desensitized, but not in normal cells was isoprenaline-induced cAMP formation significantly enhanced by 8-Br-cAMP pretreatment. This may indicate that beta-adrenoceptors which appear during 8-Br-cAMP exposure are poorly coupled to the adenylate cyclase. Alternatively, the change in receptor density may be accompanied by alterations of other components in the beta-adrenergic system, e.g. an inhibition of the adenylate cyclase. We suggest that cAMP-dependent feed-back regulation of the beta-adrenergic system may play a role during postnatal myocardial differentiation.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1984

Dihydropyridine derivatives prolong the open state of Ca channels in cultured cardiac cells.

The dihydropyridine derivatives CGP 28392 and BAY K 8644 exert a strong positive inotropic effect in mammalian cardiac muscle, presumably by increasing Ca influx during the action potential. Analysis of the drug effects at the level of single Ca channels by means of the patch-clamp method revealed complicated changes in the kinetics of channel gating. The prevailing effect is a prolongation of the mean open time of Ca channels. In addition, the intervals between channel openings can be slightly prolonged. Ensemble averages of single-channel traces showed a concentration-dependent increase in the mean current amplitude by the drugs. In contrast to beta-adrenoceptor agonists, the increase in Ca current by the dihydropyridine derivatives is not associated with an increase in the intracellular cyclic AMP level.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1983

Zeolithe A--A phosphate substitute for detergents: toxicological investigation.

Tests on Zeolithe A, a sodium aluminium silicate developed as a substitute for phosphates in detergents, were designed to investigate the safety of exposure to the material, or to detergents containing it, either under industrial conditions encountered during manufacturing processes or as a consequence of domestic use. The test programme included oral studies (acute, subchronic and long-term carcinogenicity tests and absorption measurements), and dermal, ocular and inhalation studies on the silicate alone and on appropriate detergent formulations, as well as studies of possible silicogenic activity and metal-complexing potential and measurements of dust generation and particle-size distribution. These studies did not produce any evidence to suggest that levels of domestic and industrial exposure resulting from the projected use of Zeolithe A in detergents would present any hazard to health. Zeolithe A did not induce silicotic tissue reactions and when incorporated into detergent formulations did not increase the liberation of fine dusts.

Administration, Oral↗
PubMed1983

Sodium channels in cultured cardiac cells.

Primary cardiac cell cultures were prepared from the hearts of neonatal rats. The patch-clamp method (Hamill, Marty, Neher, Sakmann & Sigworth, 1981) was applied for studying whole-cell Na+ currents and single-channel Na+ currents, respectively. Whole-cell recordings yielded voltage- and time-dependent Na+ currents which could be blocked by tetrodotoxin. Single-channel Na+ currents were directly compared in cell-attached patches and in inside-out patches. In cell-attached patches the elementary current was about -1 pA at -10 mV and the slope conductance over a 50 mV voltage range was 15.1 +/- 1.6 pS (mean +/- S.D.). Inactivation during depolarization and after conditioning clamp steps, in the steady state, resulted from a reduced opening probability of Na+ channels. In inside-out patches, with identical solutions at both membrane surfaces, there was a large (40-50 mV) shift of channel opening and inactivation kinetics towards more negative potentials. However, for levels of comparable opening probabilities, mean open times of Na+ channels were similar in cell-attached and inside-out patches. Tetrodotoxin (10-20 microM) had no effect on Na+ channels when applied from the inside, but blocked them completely after application to the outside membrane surface.

Action Potentials↗
PubMed1983

Studies of the persorption of large particles from radio-labelled cation exchangers.

Experiments were carried out in pigs to ascertain to what extent the cation exchangers Ujolyt and Campanyl used in the prevention of urinary stones undergo persorption and appear in the urine. We used two preparations of different grain size and detected them by labelling with 35S. A maximum of 0.5% or 5 X 10(-3) of the dose was found as persorbed particles at 51 h, chiefly in the muscles. The number of persorbed particles from the fine-grained preparation was considerably greater than that from the coarse-grained product. The urine contained the smallest proportion of particles, less than 2 X 10(-5) of the dose. In view of these results there is no reason to believe that solid particles persorbed during treatment with ion exchange resins can act as crystallization centres for stone formation, and it is equally unlikely that ion exchangers have to reach the urine before they can exert their effect.

Animals↗