Extracellular Magnesium Concentration Research Articles

Comments on the kinetics and extracellular effects of potassium and magnesium

Potassium and magnesium are important electrolytes which have to be ingested in sufficient amounts. They differ in the necessary daily intake (about 100 mmol potassium, about 12 mmol magnesium), the degree of intestinal absorption (potassium almost 100%, magnesium about 30%) and the distribution between the extracellular and intracellular space. If there is a deficiency in potassium or magnesium, it is necessary to substitute these materials. Deficiency of potassium is not rarely combined with deficiency of magnesium. The concentration gradient between intra- and extracellular potassium mainly determines the resting membrane potential of the cell. Lower extracellular potassium may lead to an instable membrane potential because of a decrease in potassium conductance. An increase in extracellular potassium concentration leads to the depolarization of the cell. Extracellular potassium activates the sodium potassium pump and thereby prevents an increased intracellular accumulation of sodium and calcium. Important effects of extracellular magnesium are: calcium antagonism, increase of excitation threshold and inhibition of transmitter release. By increasing the plasma concentration of magnesium, it is possible to exert pharmacodynamic effects. An increase above the normal range usually is only possible by parenteral application. However, a slight elevation can already be achieved by oral application. This increase may lead to limited pharmacodynamic effects. By elevation of the extracellular magnesium concentration, adverse, depolarisation-dependent effects of an increase in extracellular potassium concentration (for example slowing of conduction of excitation) can be compensated. This effect can be explained by a magnesium-dependent decrease of the membrane surface potential.

Whole-cell NMDA-evoked current in suprachiasmatic neurones of the rat: modulation by extracellular calcium ions

The action of N-methyl- d-aspartic acid (NMDA) on suprachiasmatic neurones was studied using whole-cell recordings in coronal hypothalamic slices of the rat. The location of the recorded neurones within the suprachiasmatic nucleus was ascertained by intracellular labelling with biocytin, followed by histological processing of the slice. Suprachiasmatic neurones had an input resistance of 780±20 M Ω (mean±S.E.M.; n=106). They were voltage-clamped at or near their resting membrane potential and their responsiveness to NMDA was tested by adding this compound to the perfusion solution. NMDA generated an inward current in about 85% of the neurones. At 50 μM, the average induced peak current was 30±10 pA ( n=32); at 100 μM, it was 50±10 pA ( n=12). The NMDA-induced current was reduced by d-2-amino-5-phosphopentanoic acid (D-AP5), an NMDA receptor antagonist, and was suppressed by MK-801, an NMDA channel blocker. Reducing the extracellular magnesium concentration from 1 to 0.01 mM caused a 2- to 3-fold increase in the amplitude of this current. Thus, suprachiasmatic neurones are endowed with functional NMDA receptor-channels, which may play a role in glutaminergic transmission in this nucleus. Decreasing the extracellular calcium concentration from 2 to 0.01 mM caused a 1.3- to 4.5-fold enhancement in the whole-cell NMDA current. This effect was probably not mediated by a change in the intracellular free calcium concentration. Indeed, loading suprachiasmatic neurones with 11 or 20 mM of the calcium chelator, 1,2- bis(2-aminophenoxy)ethane- N,N,N′,N′-tetracetic acid (BAPTA) suppressed a calcium-dependent slowly decaying outward aftercurrent but did not affect the low-calcium-induced facilitation of the NMDA response. NMDA current–voltage relations were established in normal and low-calcium perfusion solutions. In the normal solution, the net current generated by NMDA contained a region of negative slope conductance and reversed in polarity at 7±2 mV. In the low-calcium solution, this current increased in amplitude in the region of negative slope conductance, whereas at more depolarized potentials it was not altered. The NMDA-induced current was fitted using the Boltzmann equation. The effect of a low-calcium solution could be modelled by shifting the activation of the NMDA-sensitive conductance in the negative direction, by about 17 mV. We conjecture that lowering external calcium can unmask negative surface charges located on or near the NMDA channel and that this, in turn, weakens the voltage-dependent block of the channel by magnesium. A voltage-dependent blockade of the NMDA channel by calcium, however, may also contribute to this effect. This low-calcium-induced facilitation of the NMDA response could play a regulatory role by enhancing calcium influx through the NMDA channel in case of calcium depletion in its vicinity.

Endothelin-1-induced contraction in isolated aortae from normotensive and DOCA-salt hypertensive rats: effect of magnesium.

1. The contractile responses to endothelin-1 and the effect on these of various magnesium concentrations, were studied in isolated aortic rings from normotensive Sprague-Dawley rats and deoxycorticosterone acetate-salt (DOCA-salt) hypertensive rats. 2. Contractions induced by endothelin-1 were smaller in endothelium-denuded aortae from DOCA-salt hypertensive rats than in those from normotensive rats. The absence of calcium in the medium attenuated endothelin-1-induced contractions of aortae from both normotensive and DOCA-salt rats, but the contraction was greater in aortae from DOCA-salt hypertensive rats. Ryanodine (which inhibits the release of intracellular calcium) inhibited endothelin-1-induced contractions in aortae from DOCA-salt hypertensive rats to a greater extent than in aortae from normotensive rats. 3. A high extracellular magnesium concentration (4.8 mM) attenuated endothelin-1-induced contractions in tissues from DOCA-salt hypertensive rats but not in tissues from normotensive rats. In the absence of calcium, a high concentration of magnesium attenuated endothelin-1-induced contraction in aortae from both normotensive and hypertensive rats. In the presence of ryanodine, a high concentration of magnesium did not modify the contraction in preparations from either strain. 4. Absence of magnesium attenuated endothelin-1-induced contractions in aortae from both normotensive and DOCA-salt hypertensive rats. In the absence of calcium, removal of magnesium totally inhibited endothelin-1-induced contraction in tissues from normotensive rats but had no effect in those from hypertensive rats. In the presence of ryanodine, the lack of magnesium inhibited endothelin-1-induced contractions in aortae from DOCA-salt hypertensive rats but increased the sensitivity to endothelin-1 of aortae from normotensive rats. 5. The presence of endothelium did not modify the effect of high magnesium on endothelin-1-induced contractions in aortae from normotensive and DOCA-salt hypertensive rats. Conversely, the attenuating effect of magnesium removal on endothelin-1-induced contractions did not occur when endothelium was present. 6. In conclusion, endothelin-1-induced contraction was blunted in aortae from DOCA-salt hypertensive rats. The blunted response was related to altered calcium utilization during contraction. Changes in extracellular magnesium concentration differentially alter endothelin-1-induced contraction in aortae from normotensive and hypertensive rats, possibly by interfering with calcium utilization during contraction. Magnesium may be required for the contractile response to endothelin-1 and increasing magnesium may limit the vascular effects of endothelin-1 in blood vessels from DOCA-salt hypertensive rats.

A field potential analysis on the effects of lamotrigine, GP 47779, and felbamate in neocortical slices.

We studied the action of the new antiepileptic drugs lamotrigine (LTG), GP 47779 (the active metabolite of oxcarbazepine), and felbamate (FBM) on stimulus-evoked field potentials recorded from rat prefrontal and frontal cortical slices. In the presence of physiologic concentrations of extracellular magnesium (1.2 mM) the field potential amplitude was not affected by the N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, 2-amino-5-phosphonovalerate (APV), while it was blocked by the non-NMDA glutamate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). When magnesium was removed from the bathing medium, there was a significant NMDA-mediated component of the field potential. LTG and GP 47779 decreased, in a dose-dependent manner, the field potential amplitude under both experimental conditions. FBM caused a dose-related decrease of the field potential amplitude only in the absence of external magnesium, suggesting a selective interaction with an NMDA-mediated component of this potential. These findings indicate that the reduction of cortical excitatory transmission might represent a common target for new antiepileptic drugs.

High extracellular calcium stimulates osteoclast-like cell formation and bone-resorbing activity in the presence of osteoblastic cells.

The present study was performed to examine the effect of the high concentration of extracellular calcium ([Ca2+]e) on osteoclast-like cell formation and bone-resorbing activity in the presence or absence of osteoblasts. High [Ca2+]e (3 and 5 mM) significantly stimulated osteoclast-like cell formation in osteoblast-containing mouse bone cell cultures, although high [Ca2+]e did not affect the formation of osteoclast-like cells from hemopoietic blast cells supported by granulocyte-macrophage colony-stimulating factor in mouse spleen cell cultures. The osteoclast-like cells, newly formed by high [Ca2+]e in the presence of osteoblasts, possessed the ability to form pits on the dentine slices. The conditioned medium from osteoblastic MC3T3-E1 cells treated with high [Ca2+]e (5 mM) significantly increased the formation of osteoclast-like cells from hemopoietic blast cells, compared with the control medium. Dantrolene, an inhibitor of calcium mobilization from the intracellular calcium pool, and indomethacin significantly blocked high [Ca2+]e-stimulated osteoclast-like cell formation in the presence of osteoblasts, although voltage-dependent calcium channel blockers and anti-insulin-like growth factor I antibody did not affect it. High [Ca2+]e, however, significantly stimulated the bone-resorbing activity of mature osteoclasts in osteoblast-containing mouse bone cell cultures, although high [Ca2+]e inhibited bone-resorbing activity in isolated rabbit osteoclasts. An increase in the extracellular magnesium concentration (5 mM) affected neither osteoclast-like cell formation nor bone-resorbing activity. In conclusion, high [Ca2+]e stimulated osteoclast-like cell formation and bone-resorbing activity of mature osteoclasts, presumably via osteoblasts.

Electromyographical Ischemic Test and Intracellular and Extracellular Magnesium Concentration in Migraine and Tension‐Type Headache Patients

Headache has often been described in the hyperexcitability syndrome which recognizes an alteration of calcium and magnesium status in its etiopathogenesis. Moreover, in migraine patients magnesium has been shown to play an important role as a regulator of neuronal excitability and, therefore hypothetically, of headache. The present research involves a neurophysiological evaluation and magnesium status assessment of a group of headache patients. Nineteen patients (15 women and 4 men) with episodic tension-type headache and 30 patients (27 women and 3 men) with migraine without aura were examined. An ischemic test was carried out on the right arm with electromyographic (EMG) recording of motor unit potential activity during the interictal period. The determination of extracellular (serum and saliva) and intracellular (red and mononuclear blood cells) magnesium was also performed. The EMG test was positive in 25 of 30 migraine patients and in 2 of 19 tension-type headache patients. Between the two patient groups, there were no significant variations in the concentration of extracellular and white blood cell magnesium, while the red blood cell concentration of this mineral in the group of migraineurs was significantly reduced with respect to that in the group of tension-type headache patients (P < 0.05). The positive EMG test was significantly associated with a low concentration of red blood cell magnesium (P < 0.0001). These results confirm previous findings by demonstrating different etiopathogenic mechanisms as the basis of migraine and tension-type headache. Migraine seems to be related to an altered magnesium status, which manifests itself by a neuromuscular hyperexcitability and a reduced concentration in red blood cells.

The mechanisms of generation and propagation of synchronized bursting in developing networks of cortical neurons

The characteristics and mechanisms of synchronized firing in developing networks of cultured cortical neurons were studied using multisite recording through planar electrode arrays (PEAs). With maturation of the network (from 3 to 40 d after plating), the frequency and propagation velocity of bursts increased markedly (approximately from 0.01 to 0.5 Hz and from 5 to 100 mm/sec, respectively), and the sensitivity to extracellular magnesium concentration (0-10 mM) decreased. The source of spontaneous bursts, estimated from the relative delay of onset of activity between electrodes, varied randomly with each burst. Physical separation of synchronously bursting networks into several parts using an ultraviolet laser, divided synchronous bursting into different frequencies and phases in each part. Focal stimulation through the PEA was effective at multiple sites in eliciting bursts, which propagated over the network from the site of stimulation. Stimulated bursts exhibited both an absolute refractory period and a relative refractory period, in which partially propagating bursts could be elicited. Periodic electrical stimulation (at 1 to 30 sec intervals) produced slower propagation velocities and smaller numbers of spikes per burst at shorter stimulation intervals. These results suggest that the generation and propagation of spontaneous synchronous bursts in cultured cortical neurons is governed by the level of spontaneous presynaptic firing, by the degree of connectivity of the network, and by a distributed balance between excitation and recovery processes.

Cooperative effects of neuronal ensembles.

Electrophysiological properties of neurons as the basic cellular elements of the central nervous system and their synaptic connections are well characterized down to a molecular level. However, the behavior of complex noisy networks formed by these constituents usually cannot simply be derived from the knowledge of its microscopic parameters. As a consequence, cooperative phenomena based on the interaction of neurons were postulated. This is a report on a study of global network spike activity as a function of synaptic interaction. We performed experiments in dissociated cultured hippocampal neurons and, for comparison, simulations of a mathematical model closely related to electrophysiology. Numeric analyses revealed that at a critical level of synaptic connectivity the firing behavior undergoes a phase transition. This cooperative effect depends crucially on the interaction of numerous cells and cannot be attributed to the spike threshold of individual neurons. In the experiment a drastic increase in the firing level was observed upon increase of synaptic efficacy by lowering of the extracellular magnesium concentration, which is compatible with our theoretical predictions. This "on-off" phenomenon demonstrates that even in small neuronal ensembles collective behavior can emerge which is not explained by the characteristics of single neurons.

Modulation of stimulus-secretion coupling by various extracellular magnesium concentrations in rat parietal cells: F.Ch. Mooren, R. Stoll, E. Spyrou, R. Schlotmann, W. Beil+ and W. Domschke, Dept. of Medicine B, University of Münster, and +Dept. of General Pharmakology, Hannover Medical School, 30625 Hannover, Germany

Modulation of stimulus-secretion coupling by various extracellular magnesium concentrations in rat parietal cells: F.Ch. Mooren, R. Stoll, E. Spyrou, R. Schlotmann, W. Beil+ and W. Domschke, Dept. of Medicine B, University of Münster, and +Dept. of General Pharmakology, Hannover Medical School, 30625 Hannover, Germany

Original article: Effects of Raised Extracellular Magnesium on Platelet Reactivity

The inhibitory effects on platelet reactivity of increased extracellular magnesium were investigated. Wherever possible, experiments were performed in hirudinized whole blood. Concentration dependent inhibition of platelet aggregation and dense granule release were observed with MgSO(4). Antiaggregatory effects were identical with MgCl(2), indicating that the effects are due to the Mg(2+) ion. Antiaggregatory effects of CaCl(2), differed from those of MgCl(2), indicating that this is not a non-specific divalent cation effect. MgSO(4) also caused concentration-dependent inhibition of platelet thromboxane production. Experiments in the presence of apyrase and indomethacin showed that complex formation with ADP and inhibition of cyclo-oxygenase do not entirely account for the inhibitory effect of magnesium on platelet activation. Studies with an anti-GPIIb/IIIa antibody showed that the inhibitory effects on the release reaction and thromboxane synthesis are independent of those on aggregation. The results are consistent with magnesium modifying an intracellular signal transduction pathway common to several agonists, rather than the effects of magnesium being specific for one agonist. This study also shows that MgSO(4) inhibits agonist-induced increases in intracellular free calcium. Increasing the extracellular concentration of magnesium up to 10 mM had no effect on agonist-induced increments in intraplatelet free Mg(2+) concentration.

Leukocytes and Antibody Titers Related to Intra- and Extracellular Magnesium Concentrations

Leukocytes and Antibody Titers Related to Intra- and Extracellular Magnesium Concentrations

High Magnesium Concentration Inhibits Ligand-Stimulated Calcium Influx and Hormone Secretion in Rat Pituitary Lactotropes with Involvement of Intracellular Free Magnesium

The effects of extracellular magnesium concentration ([Mg2+]ex) on thyrotropin-releasing hormone (TRH)-stimulated intracellular free calcium mobilization and prolactin secretion were investigated concomitantly with measurement of the intracellular free magnesium concentration ([Mg2+]i). TRH-stimulated intracellular free calcium mobilization was significantly inhibited when the medium was replaced by high Mg2+ medium ([Mg2+]ex=10mM) in normal Ca2+ medium. The inhibitory effects of high Mg2+ became apparent concomitantly with an increase in [Mg2+]i from 0.7 to 1.3 mM. High Mg2+ significantly inhibited TRH-induced PRL secretion in a dose-dependent manner in normal Ca2+ medium. TRH-stimulated inositol triphosphate (IP3) production was rather augmented by the replacement with high Mg2+ medium. In summary, high Mg2+ inhibits Ca2+ influx stimulated by TRH in the rat pituitary lactotropes, possibly with the involvement of [Mg2+]i increase. These results have general importance in relation to high Mg2+-induced suppression of the biological functions of cells.

Extracellular and intracellular magnesium concentrations in asthmatic patients

Magnesium deficiency is associated with increased contractility of smooth muscle cells. Since contractility of bronchial smooth muscle is important in patients with asthma, magnesium deficiency could negatively influence the clinical condition. We wanted to assess whether magnesium deficiency exists in patients with asthma. Extracellular (plasma) and intracellular (erythrocytes and mononuclear leucocytes) concentrations of magnesium were determined in 20 mildly symptomatic patients with asthma and compared to 20 healthy controls. In asthmatic patients, the mean +/- SD magnesium level in plasma was 0.81 +/- 0.05 mmol.l-1, in erythrocytes 0.20 +/- 0.02 fmol.cell-1, and in mononuclear leucocytes 5.10 +/- 2.55 fmol.cell-1; these values did not differ significantly from those of the healthy controls: 0.79 +/- 0.06 mmol.l-1, 0.19 +/- 0.02 fmol.cell-1, and 4.61 +/- 1.75 fmol.cell-1, respectively. No evidence for the existence of a magnesium deficit needing chronic magnesium supplementation was, thus, found in these patients.

Development of connections by axons growing through injured spinal cord of neonatal opossum in culture.

The ability of neurites to grow through a lesion and form synaptic connections has been analyzed in a developing mammalian spinal cord in vitro. After isolation of the entire central nervous system (CNS) of the newly born South American opossum (Monodelphis domestica) the spinal cord was crushed. Outgrowth through and beyond the lesion was observed in living preparations for 2-5 days by staining axons with carbocyanine dyes. The structure of the acute crush and the growing neurites was examined by light and electron microscopy in tissue fixed immediately after the crush had been made. All axons had been severed and the site was filled with debris and amorphous vesicular structures. By 3 days after injury, numerous labelled neurites had grown into the lesion; by 4 days, many had extended several millimetres beyond it. At this time normal axonal profiles were apparent in electron micrographs of the crush site. Although fewer axons grew across the lesion than had been severed by the crush, the amplitudes of compound action potential volleys conducted across the crush in injured preparations were comparable with those recorded from uninjured spinal cords. Physiological experiments made with raised concentrations of extracellular magnesium in the culture fluid indicated that growing axons had formed synaptic connections. Thus, delayed major peaks of the response were abolished while the small component corresponding to through conduction remained unaffected by magnesium. These experiments demonstrate the development of synaptic interactions by the growing neurites and confirm the far greater powers of repair in neonatal mammals compared to adults. They set the stage for comparing molecular mechanisms involved in development and regeneration of the mammalian CNS.

The actions of extracellular magnesium on isolated human detrusor muscle function.

The effects of increasing the extracellular magnesium concentration ([Mg]) on the in vitro mechanical and electrophysiological properties of isolated human detrusor smooth muscle have been investigated. Raising extracellular Mg reduced the magnitude of the electrically-induced phasic contractions as well as spontaneous contractions. A similar increase in the [Mg] reduced the magnitude of the inward Ca2+ current associated with the action potential as well as shifting the activation curve to more positive potentials. Spontaneous oscillations of intracellular Ca2+ could be observed in some isolated cells and such activity was also abolished by raising the extracellular [Mg]. It is proposed that the contractile effects of raised extracellular Mg are mediated by an action on the inward Ca2+ current and that these observations suggest a means whereby normal and abnormal detrusor contractions might be effectively regulated.

Role of endothelium in the response of the vein wall to magnesium withdrawal

Complete absence of magnesium has a two-fold effect on the arterial tone: direct smooth muscle contraction and relaxation via endothelium-derived relaxing factor (EDRF) release. In the present study performed on a systemic vein we investigated (1) which of these effects dominates following reduction of magnesium concentration from 1.2 mM to 0.8 and 0.4 mM and (2) whether the vessel segments asymmetrically respond when the magnesium concentration is reduced on either the intra- or extraluminal side. The effects of reducing magnesium concentration on both the isometric tension of isolated ring preparations and the diameter of isolated, perfused and superfused feline femoral veins were investigated. In noradrenaline-precontracted rings, rapid decreases in the extracellular magnesium concentration from 1.2 mM to 0.8 and 0.4 mM caused relaxation, whereas total omission of magnesium returned the tone to the level of the initial tone induced by noradrenaline. Both in the presence of haemoglobin (5 x 10(-6) M), and in vessels without endothelium, lowering the magnesium concentration caused a dose-dependent elevation of the noradrenaline-induced tone. In perfused and superfused noradrenaline-contracted vein segments, each reduction of extraluminal magnesium concentration caused contraction of the vessels, regardless of whether the endothelium was intact or not. A decrease in intraluminal magnesium concentration did not alter the diameter of the vessel when the endothelium was intact, but caused contraction when the endothelium was disrupted. The results of the present study demonstrate that both the reduction of magnesium concentration or its complete absence cause an EDRF-mediated relaxation and a directly mediated smooth muscle contraction in the femoral vein of the cat.(ABSTRACT TRUNCATED AT 250 WORDS)

NMDA-receptor-mediated sensory responses of brain noradrenergic neurons are suppressed by in vivo concentrations of extracellular magnesium.

Recent studies reveal at least three receptor subtypes for excitatory amino acid (EAA) neurotransmitters. Activation of one of these, the N-methyl-D-aspartate (NMDA) receptor-channel complex, has been strongly implicated in neuronal mechanisms of several important brain processes, including learning and memory. As NMDA receptors are highly sensitive to extracellular magnesium (Mg++), we tested whether in vivo concentrations of this ion are sufficient to suppress NMDA-receptor-mediated responses. We show that slow, local microinfusion of Mg(++)-free artificial cerebrospinal fluid onto noradrenergic locus coeruleus (LC) neurons reveals an NMDA-receptor-mediated component of their response to a sensory stimulus. This is the first demonstration that the in vivo concentration of extracellular Mg++ ions suppresses synaptically mediated NMDA receptor activation. We also present evidence that unmasking this NMDA receptor activity induces prolonged enhancement of the EAA-mediated sensory response of LC neurons.

Serum and salivary magnesium levels in migraine and tension-type headache. Results in a group of adult patients.

It has been suggested that magnesium plays a central role in different etiopathogenetic conditions involved in the onset of migraine. We measured, by atomic absorption spectrophotometry, serum and salivary magnesium levels in drug-free migraine patients with and without aura and in tension-type headache patients. Migraine sufferers with and without aura and tension-type headache had significantly lower levels of serum and salivary magnesium concentrations in the interical periods than a group of healthy young individuals. Serum magnesium levels tended to be further reduced during attacks in all patient groups studied. A statistically significant decrease in salivary magnesium levels was evident only for migraine patients with aura. Serum magnesium levels and to a lesser extent salivary magnesium levels might express indirectly the lowering of brain extracellular magnesium concentration which occurs in migraine patients both in the intererictal periods and ictally.

Extracellular magnesium concentration alters Purkinje cell responsiveness to serotonin and analogues

Binding studies have shown that divalent cations increase the affinity of 5-hydroxytrptamine 1A (5-HT 1A) receptors for ligands. The present study compared the effects of magnesium (Mg 2+) at physiologic (1.15 mM) and low (0.56 mM) concentrations on firing rate responses of cerebellar Purkinje cells induced by 5-HT and selective 5-HT 1 agonists applied by superfusion or iontophoresis. In low Mg 2+ concentrations, the inhibitory actions of 5-HT and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) but not meta-trifluoromethyl phenyl piperazine (TFMPP) on Purkinje cells were significantly reduced; whereas the excitatory actions to the physiologic agonist 5-HT were enhanced. This report demonstrates a functional role for Mg 2+ in the operation of the 5-HT 1A receptor located on Purkinje cells.

Polyarginine, polylysine, and protamine mimic the effects of high extracellular calcium concentrations on dispersed bovine parathyroid cells.

We investigated the effects of the basic peptides polyarginine, protamine, and polylysine on dispersed bovine parathyroid cells. All three peptides produced a dose-dependent inhibition of dopamine-stimulated cAMP accumulation, with half-maximal inhibition at 4 x 10(-8), 1.5 x 10(-7), 3 x 10(-7), and 2 x 10(-6) M, respectively, for polyarginine, protamine, and two preparations of polylysine of molecular weights 10,200 and 3800. The inhibition of cAMP accumulation was reversible and was blocked by preincubating the cells overnight with 0.5 micrograms/ml of pertussis toxin. The same peptides also inhibited PTH release at similar concentrations, markedly stimulated the accumulation of inositol phosphates at two- to threefold higher concentrations, and produced transient increases in the cytosolic Ca2+ concentration (Cai) in fura-2-loaded parathyroid cells. The polylysine-evoked spike in Cai persisted despite the removal of extracellular Ca2+, indicating that it arose from intracellular Ca2+ stores. Exposure of the cells to elevated extracellular magnesium (Mg2+) concentrations elicited a similar spike in Cai but blocked the Cai transient in response to subsequent addition of polylysine, or vice versa. Thus, Mg2+ and polylysine mobilize Ca2+ from the same intracellular store(s). These results indicate that highly basic peptides closely mimic the effects of polyvalent cations on parathyroid function, suggesting that both agents may regulate parathyroid function via similar biochemical pathways.