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G Droogmans

Publications and source records attributed to G Droogmans.

At least 145 records · Page 8Linked to original sources
PubMed1991

Uptake characteristics of the InsP3-sensitive and -insensitive Ca2+ pools in porcine aortic smooth-muscle cells: different Ca2+ sensitivity of the Ca2(+)-uptake mechanism.

We have investigated the Ca2(+)-uptake characteristics of the InsP3-sensitive and -insensitive non-mitochondrial Ca2+ pools in permeabilized cultured porcine aortic smooth-muscle cells. The InsP3-sensitive Ca2+ pool, which was also GTP sensitive, had a high Ca2+ affinity and was highly oxalate permeable. The InsP3-insensitive Ca2+ store, which was also GTP insensitive, had a much lower Ca2+ affinity and presented a low oxalate permeability. The loading of both pools decreased at high free [Ca2+], although these cells did not have a Ca2(+)-induced Ca2+ release mechanism. This decreased loading of the InsP3-sensitive Ca2+ pool at higher free [Ca2+] must be taken into consideration when investigating a possible Ca2(+)-inhibition of the InsP3-induced Ca2+ release. Part of the Ca2+ uptake into the InsP3-insensitive Ca2+ pool was not affected by the Ca2(+)-pump inhibitors vanadate, thapsigargin and 2,5-di-(tert-butyl)-1,4-benzohydroquinone.

Animals↗
PubMed1991

Carbachol-induced nonspecific desensitization in guinea-pig ileum.

The effects of repeated stimulation by carbachol on force development have been examined in smooth muscle of the longitudinal layer of the guinea-pig ileum. Carbachol was applied at 20 degrees C for 5 min. Each application was followed by a 25-min washout period and the desensitization was expressed by the decline of the maximal force development. Three hours after the first carbachol-induced contraction the peak amplitude was about 40% of the initial value. Increasing the frequency of application, thereby decreasing the washout time, enhanced the desensitization, while the presence of the competitive blocker atropine reduced the phenomenon. At 35 degrees C no desensitization could be observed. Blocking the Na+/K+ pump by ouabain or by K(+)-free solution reduced the force development to less than 20%. Increasing [K+]0 in the washout solution at 20 degrees C reduced the desensitization phenomenon, while decreasing [K+]0 resulted in an enhanced desensitization as expressed by a decline of the force development. The total cellular Na+ content after various stimulation sequences was determined at 20 degrees and 35 degrees C from the 22Na+ effluxes. At 35 degrees C the cellular Na+ content did not change significantly during stimulation for 10 min with 10(-4) mol/l carbachol. At 20 degrees C the resting Na+ content was significantly increased, and it doubled during carbachol stimulation for 10 min. Furthermore, the recovery of the cellular Na+ content after washout proceeded extremely slowly at that temperature. The appearance of desensitization was increased by 10 mumol/l ryanodine, while it was reduced by adding the Ca2+ agonist Bay K 8644.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

AlF4- induces Ca2+ oscillations in guinea-pig ileal smooth muscle.

The effects of different compounds that inhibit the isolated plasma-membrane Ca2+/Mg2(+)-ATPase on the cytosolic free Ca2+ concentration ([Ca2+]i) and on the corresponding force development have been examined in smooth muscle of the longitudinal layer of the guinea-pig ileum. F-, in the presence of Al3+, induced an increase of the resting force and of the amplitude of the superimposed phasic contractions. The increase of resting force was associated with an increased level of basal [Ca2+]i while the phasic contractions were accompanied by concomitant oscillations in [Ca2+]i. Comparable contractions could be induced by vanadate and the calmodulin antagonist calmidazolium. The oscillations of [Ca2+]i and of force elicited by AlF4- were not modified by adrenergic or cholinergic blocking agents but were inhibited by verapamil. These phasic contractions were not affected by depleting the intracellular Ca2+ stores with ryanodine. This finding excludes a cytosolic origin of these oscillations. However, hyperpolarization and complete depolarization of the cells inhibited the oscillations. It is concluded that AlF4-, vanadate and calmidazolium induce cytoplasmic Ca2+ oscillations possibly by acting at the plasma membrane. Indeed all these substances affect by different mechanisms the isolated plasma-membrane Ca2+/Mg2(+)-ATPase. The generation of membrane-linked Ca2+ oscillations could therefore be related to an inhibition of the plasma-membrane Ca2+ pump resulting in an increase of [Ca2+]i. This change in [Ca2+]i could be responsible for the pronounced changes of the electrical and mechanical activity of this tissue.

Aluminum↗
PubMed1991

Ca2+ extrusion across plasma membrane and Ca2+ uptake by intracellular stores.

The aim of this review is to summarize the various systems that remove Ca2+ from the cytoplasm. We will initially focus on the Ca2+ pump and the Na(+)-Ca2+ exchanger of the plasma membrane. We will review the functional regulation of these systems and the recent progress obtained with molecular-biology techniques, which pointed to the existence of different isoforms of the Ca2+ pump. The Ca2+ pumps of the sarco(endo)plasmic reticulum will be discussed next, by summarizing the discoveries obtained with molecular-biology techniques, and by reviewing the physiological regulation of these proteins. We will finally briefly review the mitochondrial Ca(2+)-uptake mechanism.

Animals↗
PubMed1991

ATP-induced Ca2+ release and Cl- current in cultured smooth muscle cells from pig aorta.

1. The effect of exogenous ATP on transmembrane currents and on the cytoplasmic Ca2+ has been investigated in single cultured smooth muscle cells of pig aorta. 2. ATP applied to cells held at a potential of -50 mV evoked a transient inward current and a transient rise in [Ca2+]i. At a potential of +20 mV the ATP-induced increase in [Ca2+]i was accompanied by an outward current. 3. At a potential of -50 mV, ATP evoked in Ca(2+)-free solution an inward current which was similar to that in the presence of external Ca2+. A second application of ATP in Ca(2+)-free solution induced a much smaller current. 4. ATP induced in Ca(2+)-free solution a pronounced transient stimulation of the 45Ca2+ efflux from confluent smooth muscle monolayers. 5. The I-V curve of the ATP-activated current has a reversal potential close to 0 mV. A reduction of external Cl- shifts this reversal potential in accordance with the change of the Cl- equilibrium potential. 6. It is concluded that ATP causes a release of calcium from intracellular stores. The ensuing increase of [Ca2+]i activates a Cl- current, which can depolarize the cell membrane and thereby promote a voltage-gated Ca2+ entry.

Adenosine Triphosphate↗
PubMed1990

Ruthenium red and compound 48/80 inhibit the smooth-muscle plasma-membrane Ca2+ pump via interaction with associated polyphosphoinositides.

We will demonstrate the compound 48/80 and ruthenium red inhibit the smooth-muscle plasma-membrane Ca2+ pump by counteracting the stimulant effect of negatively charged phospholipids. Both substances did not affect the purified enzyme re-activated by pure phosphatidylcholine or phosphatidylinositol and measured in the absence of calmodulin, indicating that under these conditions they did not have a direct effect on the ATPase protein. Ruthenium red and compound 48/80 however inhibited the (Ca2(+) + Mg2+)-ATPase in the presence of phosphatidylinositol 4-phosphate and especially phosphatidylinositol 4,5-bisphosphate. The K0.5 for inhibition was 25 microM ruthenium red and 9 micrograms/ml of compound 48/80. The inhibition by ruthenium red developed slowly with half maximal inhibition occurring after about 75 s while that by compound 48/80 developed immediately within the time required for mixing. The efficacy of ruthenium red increased as the concentration of the acidic phospholipid increased, while no such cooperativity was observed for compound 48/80. Ruthenium red reduced the Vmax for Ca2+ without affecting the affinity for Ca2+, while compound 48/80 decreased both parameters. In conclusion, although ruthenium red and compound 48/80 affect the ATPase differently, both substances most likely inhibit the plasma-membrane Ca2+ pumping by counteracting the stimulation by negatively charged phospholipids.

Animals↗
PubMed1990

The alpha 1-agonist phenylephrine inhibits voltage-gated Ca2(+)-channels in vascular smooth muscle cells of rabbit ear artery.

The effects of the alpha 1-agonist phenylephrine on the voltage-gated Ca2(+)-entry in vascular smooth muscle cells has been studied by measuring the agonist-induced changes of [Ca2+]i in K(+)-depolarized tissues. These changes have been estimated from the changes in fluorescence of the Ca2(+)-indicator fura-2, or have been assessed from the changes in 86Rb-efflux rate through Ca2(+)-activated K(+)-channels. Phenylephrine increases the force development in K(+)-depolarized tissues, but reduces [Ca2+]i and inhibits the 86Rb-efflux rate. However, in the presence of the Ca2(+)-entry blocker verapamil, phenylephrine increases both force development and [Ca2+]i. It is concluded that phenylephrine inhibits voltage-gated Ca2(+)-channels, and also induces an influx of calcium by activating a verapamil-insensitive pathway.

Animals↗
PubMed1990

Agonist-dependent Ca2+ and Mn2+ entry dependent on state of filling of Ca2+ stores in aortic smooth muscle cells of the rat.

1. The properties of intracellular Ca2+ stores of intact- and of saponin-skinned A7r5 (an established cell line from embryonic rat aorta) smooth muscle cells were studied by measuring 45Ca2+ and 54Mn2+ fluxes. 2. Application of 5 microM-vasopressin to intact cells increased the fractional loss of 45Ca2+ in Ca2(+)-free solution by a factor of 5.2. This effect was not influenced by a pre-incubation with 10 microM-ryanodine. Caffeine (25 mM) did not stimulate the fractional loss of 45Ca2+ from intact cells. 3. In skinned cells 10 microM-IP3 (inositol 1,4,5-trisphosphate) and 5 microM-A23187 (a calcium ionophore) released the same amount of 45Ca2+. This release did not require GTP and was not affected by a pre-incubation with 10 microM-ryanodine. Caffeine (25 mM) did not release stored Ca2+. 4. NaF (1 mM) plus 10 microM-AlCl3 inhibited by 72% the 45Ca2+ uptake by the IP3-sensitive store of skinned cells at 0.15 microM-Ca2+. Cyclic AMP-dependent protein kinase did not stimulate this ATP-dependent 45Ca2+ uptake, nor could the presence of phospholamban be demonstrated immunologically. 5. The 45Ca2+ uptake by cells which had been depleted of Ca2+ with 5 microM-vasopressin was 69% higher than the uptake obtained without such proceeding depletion. This enhanced 45Ca2+ uptake did not occur through voltage-operated Ca2+ channels, because blockade of these channels with verapamil, or depolarization of the plasma membrane by increasing [K+] from 5.9 to 59 mM in the presence of verapamil, did not modify this uptake. 6. A similar increase of the 54Mn2+ uptake occurred in intact cells with a depleted Ca2+ store. If, however, the cells were first skinned and subsequently exposed to 54Mn2+, the ATP-dependent 54Mn2+ uptake amounted to less than 6% of the ATP-dependent 45Ca2+ uptake. 7. If intact cells were first exposed to a 45Ca2(+)- or 54Mn2(+)-containing solution, and subsequently skinned in a non-radioactive intracellular solution, the addition of 10 microM-A23187 to these cells released stored Ca2+ or Mn2+. The amount of released Ca2+ was only slightly larger than the amount of released Mn2+. If the intracellular store was depleted before loading, the amount of Ca2+ or Mn2+ released by the ionophore increased by 68 and 28%, respectively. 8. It is concluded that A7r5 smooth muscle cells do not express a Ca2(+)-induced Ca2+ release mechanism, but do contain an IP3-induced Ca2+ release mechanism which can release approximately all intracellularly accumulated 45Ca2+.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗
PubMed1989

Role of arginine residues in the stimulation of the smooth-muscle plasma-membrane Ca2+ pump by negatively charged phospholipids.

Negatively charged phospholipids strongly stimulate the purified plasma membrane Ca2+ pump of erythrocytes [Enyedi, Flura, Sarkadi, Gardos & Carafoli (1987) J. Biol. Chem. 262, 6425-6430] and of smooth muscle [Missiaen, Raeymaekers, Wuytack, Vrolix, De Smedt & Casteels, (1989) Biochem. J. 263, 687-694]. We have investigated the role of arginine residues in the interaction of these acidic phospholipids with the smooth-muscle Ca2+ transport ATPase. The arginine-modifying reagent phenylglyoxal inhiibited the ATPase activity in a time-dependent fashion by decreasing the Vmax. of the Ca2(+)-activation curve. Low concentrations of PtdIns, PtdIns4P, PtdIns(4,5) P2, phosphatidylserine and phosphatidic acid partially prevented this inactivation. This protective effect was however not apparent at higher concentrations of PtdIns4P, PtdIns(4,5) P2 and phosphatidic acid, which may be related to the previously observed inhibition of the enzyme at higher concentrations of these phospholipids. These findings indicate that the functionally important interaction of the acidic lipids with the protein occurs at least partially via arginine residue(s).

Aldehydes↗
PubMed1989

Alkalinization stimulates the purified plasma-membrane Ca2+ pump by increasing its Ca2+ affinity.

The finding that negatively charged phospholipids activate the plasma-membrane (Ca2+ + Mg2+)-ATPase and that polycations counteract this stimulation suggest that negative charges in the environment of the ATPase protein could be important for its function. The aim of the present work was to investigate whether changing the charges on the ATPase protein itself by modifying the pH within the physiological range affects the activity of the purified plasma-membrane Ca2+ pump from stomach smooth muscle. Increasing the pH from 6.9 to 7.4 and using 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid (BAPTA) as a Ca2+ buffer, doubled the ATPase activity at 0.3 microM-Ca2+ in the presence of 100% phosphatidylcholine (PC) or after substituting 20% of the PC by negatively charged phospholipids PtdIns, PtdIns4P, phosphatidylserine and phosphatidic acid. This stimulatory effect was due to an increased affinity of the enzyme for Ca2+, while the Vmax. remained unaffected. In the case of PtdIns(4,5)P2, a stimulatory effect upon alkalinization was only observed at a PtdIns(4,5)P2 concentration of 10%. When a concentration of 20% was used, alkalinization decreased the Vmax. and no stimulatory effect on the ATPase at 0.3 microM-Ca2+ could be observed. Alkalinization not only stimulated the purified Ca2+ pump, but it also increased the activity of the enzyme in a plasma-membrane-enriched fraction from stomach smooth muscle by a factor of 2.06. The ionophore A23187-induced Ca2+ uptake in closed inside-out vesicles also increased by a factor of 2.54 if the pH was changed from 6.9 to 7.4. This finding indicates that the effect of pH is most likely to be exerted at the cytoplasmic site of the Ca2+ pump protein.

Animals↗
PubMed1989

AlF-4 inhibits the accumulation of Ca in the endoplasmic reticulum in intact myometrial strips, but not in the rabbit ear artery.

AlF-4, known to be a potent modulator of G-proteins, also inhibits purified "P"-type cation-transport ATPases (Missiaen et al. 1988). The aim of the present work is to find out whether AlF-4 also inhibits these ATPases in intact cells. We therefore have studied the effect of AlF-4 on the force development and on 45Ca2+ -fluxes of muscle strips from rat myometrium and rabbit ear artery. 1 mM-NaF plus 10 microM-AlCl3 induces in both tissues a tonic contraction that is completely blocked by 0.5 mM-deferoxamine. The contractile response in myometrium exceeds that of the ear artery. These contractions are independent of an activation of G-proteins but their amplitude depends on [Ca2+]o. Application of AlF-4 during the loading of the endoplasmic reticulum of myometrium with Ca2+ dramatically reduces the amount of stored Ca2+ as estimated from its release induced by 1 mM-carbachol during incubation in Ca-free solution. This effect could be due to a predominant inhibitory effect of AlF-4 on the (Ca2+ + Mg2+)-ATPase of the endoplasmic reticulum. Such effect could not be established in rabbit ear artery. The increase of the fractional loss of 45Ca2+ induced by 10 microM-norepinephrine in rabbit ear artery is not inhibited by AlF-4. It is concluded that the inhibition of the endoplasmic-reticulum (Ca2+ + Mg2+)-ATPase in intact myometrial cells warns us against explaining all effects of AlF-4 on intact cells only by an activation of G-proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed1989

Kinetic properties of the cardiac T-type calcium channel in the guinea-pig.

1. The kinetic properties of T-type Ca2+ channels were examined in single ventricular cells from guinea-pig hearts using the cell-attached configuration of the patch-clamp technique. 2. T-type Ca2+ channel activity has been observed in 44 out of 139 patches. The density of these channels was estimated at 0.1-0.3 micron-2. The T-type Ca2+ channel responds to a depolarizing voltage step either with a burst of openings which appears with a distinct delay or with no openings at all. The mean number of bursts per record for the records showing channel activity is 1.1. The probability of observing a blank sweep is high and amounts to 0.65 +/- 0.02 (n = 26). 3. With 110 mM-Ca2+ in the pipette solution, the slope conductance calculated from the current-voltage relationship of the single-channel current in the range between -50 and +10 mV is 6.8 pS. 4. Openings to a subconductance level of about 50% of the main level could be resolved. All possible transitions between the subconductance and the main level were observed, indicating that the cardiac T-type Ca2+ channel possesses a substate. 5. The macroscopic steady-state activation and inactivation, as determined from ensemble-averaged currents, could be described by Boltzmann functions. Half-maximal activation and inactivation occur at -14 and -60.7 mV, the slope parameters of these curves are 10.8 and 5.6 mV respectively. The maximum (peak) open probability is 0.15. 6. The ensemble-averaged current decays monoexponentially. The time constant is strongly voltage dependent and decreases at less negative potentials. 7. The open times are monoexponentially distributed. The mean open time of the channel does not depend on either the holding or the test potential, and has a mean value of 1.4 ms. The distribution of the closed times is biexponential. The fast mean closed time is also voltage independent with a mean value of 0.48 ms. The slow mean closed time increases with voltage from 1.9 ms at -40 mV to 8.8 ms at 0 mV. The mean burst duration also increases with voltage from a value of 4.9 ms at -40 mV to 13.9 ms at -10 mV. 8. The convolution of the first-latency distribution with that of the burst duration closely fits the open probability calculated from the ensemble-averaged current. The mean first latency is also closely correlated with the macroscopic time constant of inactivation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Effect of adrenergic agonists on Ca2+-channel currents in single vascular smooth muscle cells.

Ca2+-channel currents have been measured in enzymatically dispersed single smooth muscle cells of the rabbit ear artery using the whole-cell patch clamp technique. Inward currents were elicited by depolarizing test pulses from a holding potential of -50 mV. These currents were activated from -30 mV onward and reached full activation around 0 mV. alpha-Adrenergic agonists did not affect the background current measured at the holding potential, but markedly reduced the peak amplitude of the voltage-activated Ca2+-channel currents. This alpha-adrenergic inhibition also occurred in cells which were internally perfused with solutions containing either 10 microM cAMP, 10 microM cGMP or 0.1 mM GTP, but became irreversible when the pipette solution contained a non-hydrolyzable GTP-analog. The action of beta-agonists on the voltage-activated Ca2+-channel currents was variable, and ranged from no effect at all to a 50% reduction of the current. It is concluded that alpha-agonists do not open receptor-operated Ca2+-channels in these smooth muscle cells. The inhibition of the voltage-activated Ca2+-currents does not seem to be mediated through changes in cyclic nucleotide levels, but might be mediated through G-proteins. Its physiological relevance remains however unclear. The action of beta-agonists is consistent with their relaxing effect, but the reason for the non-uniform response has not been elucidated.

Adrenergic Agonists↗
PubMed1987

Effect of nicorandil on the excitation-contraction coupling in smooth muscle cells of the rabbit ear artery.

The effects of nicorandil on excitation-contraction coupling in the ear artery of the rabbit have been investigated. Perivascular nerve stimulation induces excitatory junction potentials (e.j.p.'s) and action potentials, which can be inhibited by nicorandil. The inhibition of the nerve-evoked responses by nicorandil cannot be due to an effect of nicorandil on neurotransmitter metabolism because of its failure to inhibit the release of 3H-noradrenaline from the nerve terminals. The decreased excitability of the smooth muscle cells can be partially explained by the increase of K permeability, as measured by 87Rb efflux, and by the concomitant hyperpolarization of the cell membrane. Because the inhibitory action of nicorandil on the contractile responses also occurs in K-depolarized tissues in which nicorandil no longer affects the membrane potential, additional mechanisms of action have to be sought. A study of 45Ca exchange under these conditions does not suggest that this relaxing effect is mediated by changes in cytoplasmic Ca.

Action Potentials↗
PubMed1986

Ca2+-channel current and its modification by the dihydropyridine agonist BAY k 8644 in isolated smooth muscle cells.

The electrophysiological properties of single smooth muscle cells isolated from the longitudinal layer of the guinea-pig ileum were studied with the whole-cell patch-clamp technique. The finding of resting potentials between -45 and -50 mV and the occurrence of spontaneous electrical activity when K+ was the predominant intracellular cation indicated that the cells were not leaky or hyperpermeable. The existence of an inward Ca2+ current overlapping in time with an outward rectifying K+ current was demonstrated. The latter could be selectively blocked by replacing internal K+ with Cs+ and external Ca2+ with Ba2+. Depolarizations to potentials between -40 and +50 mV evoked time-dependent inward currents, with a maximum peak value between -20 and 0 mV. For depolarizations beyond +50 mV time-dependent outward currents appeared. These currents were inhibited by 0.1 mM CdCl2. The activation of the inward current showed a sigmoidal time course, and the rate of onset of the current increased at more positive potentials. Inactivation could be described by two exponentials. The threshold for activation was about -40 mV, and full activation was reached at 0 mV. Inactivation was complete near 0 mV, whereas the channels were fully available at -80 mV. The fully-activated Ca2+-channel current was strongly voltage dependent. The conductance decreased for potentials close to the reversal potential, and showed rectification for hyperpolarizing potentials. The Ca2+ agonist BAY k 8644 enhanced the Ca2+-channel current without a significant effect on its kinetics. The fully-activated current and the steady-state activation were enhanced in a rather voltage-independent way.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1985

Excitation-contraction coupling in vascular smooth muscle cells and perivascular nerve stimulation.

Smooth muscle contraction depends largely on the increase of the cytoplasmic Ca2+ concentration. This change can be brought about by the opening of voltage-dependent Ca channels or receptor operated Ca channels. Although in some vascular smooth muscle cells the addition of noradrenaline does not appreciably change the membrane potential, it is observed that stimulation of the perivascular nerve fibres elicits excitatory junction potentials and action potentials. This difference between the action of exogenous and endogenous noradrenaline could be due to either the existence of intrajunctional gamma-receptors, which differ from the extrajunctional alpha-receptors or to the release from the nerve fibres of cotransmitters together with noradrenaline. It can be concluded that the clear distinction between electromechanical coupling and pharmacomechanical coupling only applies to some experimental conditions in vitro, but that the distinction cannot be used for conditions in vivo.

Adenosine Triphosphate↗
PubMed1985

Dependence on calcium of potassium- and agonist-induced changes in potassium permeability of rabbit ear artery.

The effect of K+ depolarization and agonists on the 86Rb+ efflux from rabbit ear artery has been investigated. K+ depolarization with 59 mM-K+ induces an increase of the 86Rb+ efflux rate, which is dependent on [Ca2+]o and is correlated with the concomitant force development. This effect is largely reduced by Ca2+ antagonists, such as D-600 and Mn2+. The residual increase of the 86Rb+ efflux rate is much smaller than that predicted by the constant-field equations. Stimulation with 10(-5) M-noradrenaline or 10(-4) M-histamine induces a biphasic increase of the efflux rate. The initial transient effect is reduced in low [Ca2+]o solutions, whereas the maintained component is largely independent of [Ca2+]o. Stimulation with noradrenaline during depolarization of the tissues with K+ induces, after a transient increase of the efflux rate, an inhibition of the K+-induced increase of the efflux rate. Both phases of the noradrenaline action are due to activation of alpha-adrenoreceptors. Exposure to Ca2+-free medium induces a progressive increase of the 86Rb+ efflux rate, which reaches a new steady-state value after about 60 min. Stimulation with noradrenaline after this 60 min exposure to Ca2+-free solution no longer induces a significant effect. Stimulation with noradrenaline after shorter exposures to Ca2+-free solution immediately increases the 86Rb+ efflux to a value close to the steady-state value obtained after prolonged exposure to Ca2+-free medium. Washing out the agonist has no effect on the rate constant. It will only return to its control value after exposure to solutions containing Ca2+. This recovery of the rate constant by external Ca2+ also occurs in the presence of 1 mM-Mn2+ in the perfusion fluid. On re-exposure of the tissues in the presence of 1 mM-Mn2+ to Ca2+-free solution the rate constant of the 86Rb+ efflux increases at once to the steady-state value observed in Ca2+-free solution. This increase proceeds gradually if the tissues have been re-exposed in the absence of Mn2+. It is concluded that K+ permeability might be regulated by [Ca2+]i and that this relationship can be affected by agonists. In order to explain the effects of Ca2+-free medium on the 86Rb+ efflux we have to assume that at very low values of [Ca2+]o and [Ca2+]i the membrane permeability for K+ is modified by a different mechanism.

Action Potentials↗