Effects of strontium ions on contraction and action potential in rabbit papillary muscles. A comparison with effects of tetraethylammonium ions.

The effects of Sr2+ on contraction and action potential were studied in rabbit papillary muscles and compared with effects of tetraethylammonium (TEA+). The membrane potential was measured with KCl-filled microelectrodes and the contraction was simultaneously recorded using a mechanoelectrical transducer. A partial (90%) substitution of extracellular Ca2+ (Ca2+e) by Sr2+ produced stimulation frequency-dependent prolongation of the action potential (AP) with a dominant phase "plateau" as well as prolongation of the contraction. At low frequencies where the AP prolongation was well pronounced, the contraction became biphasic. The effect of Sr2+ on both AP and contraction was blocked by nifedipine (10 mumol/l) or by increasing Ca2+e. Ryanodine suppressed the early contraction component only. AP was prolonged to a similar extent and in the same frequency-dependent manner by TEA+ (20 mmol/l). Despite similar AP configuration, no biphasic contraction developed in the presence of TEA+. High Ca2+e (10 mmol/l) or low Na+e (70 mmol/l) suppressed the TEA+ effect on AP. The data indicate that the two components of the biphasic contraction are of different origin; the early one is activated by activator cation released from the sarcoplasmic reticulum while the late one results from the Sr2+ entry across the sarcolemma via L-type Ca2+ channels.     

Barium-induced electro-mechanical uncoupling in myocardial cells

The heart of the adult moth Hyalophora cecropia requires extracellular calcium to maintain electrogenesis as well as tension development. In this study we ask whether the processes of autorhythmicity, driven electrogenesis and tension development require calcium specifically or whether the divalent cation Ba2+ can be substituted for calcium to support these activities. Ba2+ substituted for Ca2+ in equimolar amounts caused a marked (25 mV) hyperpolarization, suppression both of pacemaker activity and of tension development in spontaneously beating semi-isolated heart cells. Heart cells bathed in Ba2+ saline and paced by action potentials (produced by external stimuli) of greatly increased amplitude, prolonged phase 2 (plateau) and increased latency, and after 30 min, no mechanical activity was observed. These changes were completely reversible when calcium was reintroduced. We conclude that Ba2+ substitution for Ca2+ is an effective electromechanical uncoupler in moth heart cells. Although Ba2+ can support electrogenesis, it cannot replace 'trigger'-Ca2+ needed to release calcium from sarcoplasmic stores to effect tension development.     

Effect of Bay K 8644 on tetraethylammonium-induced excitability of the rabbit pulmonary artery

The effect of Bay K 8644 on the electrical activity of the smooth muscle cells in the main pulmonary artery of the rabbit was examined. In normal physiological solution, the resting membrane potential was -56 +/- 0.6 mV, and the cells were electrically quiescent. Tetraethylammonium (5 mM) depolarized the membrane to about -45 mV, and electrical stimulation elicited action potentials. To suppress contractile responses and thereby facilitate sustained impalements, the muscle strips were bathed with a hypertonic solution containing sucrose. The mean amplitude of the tetraethylammonium-induced action potentials in the hypertonic solution was 35 +/- 0.9 mV. The action potentials were dependent upon the extracellular Ca2+ concentration and were abolished by diltiazem (10(-6) M). Spontaneous action potentials were occasionally generated in the presence of tetraethylammonium alone and could be induced by the further addition of Ba2+ (0.5 mM). The Ca2+ agonist Bay K 8644 (10(-8) to 10(-6) M) had no effect on the resting membrane potential or excitability in normal solution. However, in the hypertonic solution containing tetraethylammonium, Bay K 8644 caused a further depolarization and oscillatory potential changes, which were not prevented by tetrodotoxin. The oscillations were suppressed or abolished by diltiazem or nilvadipine. Thus, active responses can occur in the normally quiescent smooth muscle cells of the rabbit pulmonary artery when the outward K+ current(s) are suppressed.     

Effect of calcium entry blockade on the actions of phenylephrine on the taenia of the guinea pig caecum

The interaction between phenylephrine and calcium entry blockers was studied on the taenia of the guinea-pig caecum using the double sucrose gap method. Sustained hyperpolarization, relaxation and attenuation of evoked electrical and mechanical activity were induced by non-cumulative addition of phenylephrine (0.1 to 250 mumol.1-1) for 2 to 4 min. When the alpha 1-adrenoceptor agonist was applied for a prolonged period (20 to 60 min) the initial inhibitory response gradually disappeared both at room temperature and at 32 degrees C. The renewed action potentials were accompanied by a positive afterpotential. The initial hyperpolarization and its delayed recovery in course of the phenylephrine effect were significantly reduced in calcium-free medium containing EDTA (2 mmol.1-1), after pretreatment with nifedipine (0.1 to 1 mumol.1-1), verapamil (10 to 100 mumol.1-1) or procaine (0.5 to 2 mmol.1-1). In contrast sodium nitroprusside (10 to 100 mumol.1-1) which produced biphasic changes similar to those of phenylephrine, did not affect the initial and delayed phase of phenylephrine action. Ba2+(5 mmol.1-1) could substitute for Ca2+ in the generation of action potentials but could not substitute for Ca2+ in the mechanisms responsible for the initial and delayed recovery phase of phenylephrine effects. In the presence of La3+ and Mn2+ (0.5 to 3 mmol.1-1) the phenylephrine effects were reduced. In contrast, in the presence of extracellular Ca2+, pretreatment with Mg2+ (12 mmol.1-1) or Ba2+ (5 mmol.1-1) did not affect the action of phenylephrine. It is concluded that activation of alpha 1-adrenoceptors results in the release of Ca2+ from an intracellular store, which leads to the opening od TEA-sensitive potassium channels, causing the initial phase of alpha 1-adrenoceptor action. Ca2+ is loaded into this intracellular store by entering the cell through the potential sensitive calcium channels. Although the mechanisms responsible for the delayed phase could not be clarified, its dependence on the presence of the initial phase is apparent.     

Modulating action of barium and other ions on the sensory activity of frog labyrinth

The effect of Ba2+, TEA, 4-AP and CoCl2 on the EPSP and spike discharges recorded from single fibres of the posterior nerve in the isolated frog labyrinth has been investigated. In Ca-free solution Ba2+ preserved, at low concentration (0.3 mM), the resting activity and at higher levels (up to 6 mM) it resulted in a pronounced facilitation of the EPSP and spike discharges. Facilitation increased on increasing Ba2+ concentration up to 4-5 mM and it was more evident in those units exhibiting a low resting spike firing. The effect of Ba2+ (1 mM) was completely antagonized by 10 mM Ca2+ X CoCl2 (3 mM) suppressed the resting rate at the normal external Ca2+ concentration; the Co2+ block was partially relieved by 1.8 mM Ba2+ X TEA (20 mM) evoked a clear-cut increase in the EPSP and spike discharges which, however, was less consistent than that produced by Ba2+. By comparing the effect of TEA on the spike frequency with that obtained at different Ba2+ levels, the Ba2+ capacity to carry the Ca2+ current was dissected. Such an effect is dose-dependent and it is more evident in low-frequency units. Conversely, 4-AP did not affect the resting discharge frequency. These results indicate that either the Ca2+ or the Ba2+ current sustain the transmitter release at the cyto-neural junction. The effect of TEA suggests that the Ca2+-dependent K+ current may play an important role in supporting the neurosecretory process by controlling the membrane potential of the hair cells.     

Activation of the fast calcium input in the denervated smooth muscle of the cat nictitating membrane

The excitation and contraction features of innervated and sympathetically denervated smooth muscle strips from cat's nictitating membrane have been studied by single sucrose gap arrangement. Increasing of smooth muscle cells sensitivity to drugs were accompanied by elevation of membrane response and the ability to generation of action potentials. Action potentials have been induced by agonists or high potassium concentration in external solution and spontaneously. In innervated muscle action potentials have been evoked as a result of depolarization by high potassium concentration of TEA blockade of potassium conductance. Induced and spontaneously generated action potentials were blocked by organic and inorganic antagonists of potential dependent Ca++ channels. In Ca-free solution action potentials were absent but might be supported by Ba++. Decrease of Na+ had no effect on smooth muscle excitability. It is supposed that activation of potential depended Ca++ channels in smooth muscle cells with pharmaco-mechanical coupling are under influence of sympathetic nerves.     

Steady-state currents through voltage-dependent, dihydropyridine-sensitive Ca2+ channels in GH3 pituitary cells.

Ca2+ influx via voltage-dependent Ca2+ channels is known to be elicited during action potentials but possibly also occurs at the resting potential. The steady-state current through voltage-dependent Ca2+ channels and its role for the electrical activity was, therefore, investigated in pituitary GH3 cells. Applying the recently developed 'nystatin-modification' of the patch-clamp technique, most GH3 cells (18 out of 23 cells) fired spontaneous action potentials from a baseline membrane potential of 43.7 +/- 4.6 mV (mean +/- s.d., n = 23). The frequency of action potentials was stimulated about twofold by Bay K 8644 (100 nM), a Ca(2+)-channel stimulator, and action potentials were completely suppressed by the Ca(2+)-channel blocker PN 200-110 (100 nM). Voltage clamping GH3 cells at fixed potentials for several minutes and with 1 mM Ba2+ as divalent charge carrier, we observed steady-state Ca(2+)-channel currents that were dihydropyridine-sensitive and displayed a U-shaped current-voltage relation. The results strongly suggest that the observed long lasting, dihydropyridine-sensitive Ca(2+)-channel currents provide a steady-state conductivity for Ca2+ at the resting potential and are essential for the generation of action potentials in GH3 pituitary cells.     

Action of tetanus toxin on cholinergic neuroblastoma X glioma hybrid cells: selective blockade of Ca spikes

We examined the effect of tetanus toxin on clonal neuroblastoma X glioma hybrid cells, NG108-15, by intracellular microelectrode studies of passive membrane electrical properties and action potentials generated under various conditions. Binding of tetanus toxin to the surface of the cells was demonstrated by indirect immunofluorescent staining but no morphological alteration was observed in tetanus toxin-treated cells under a phase contrast microscope. These is no significant difference between the tetanus toxin-treated and untreated cells in their passive electrical membrane properties, i.e. resting membrane potentials, input resistances, time constants and input capacities. Cells in 120 mM Na+, 2 mM Ca2+ salt solution showed Na spikes, and cells in high Ca2+ (30 mM), Na+-free salt solution showed Ca spikes in response to depolarizing current pulses. While the Na spike was not affected by tetanus toxin, the Ca spike was blocked by the toxin. The minimum dose of tetanus toxin for maximum suppression of the peak potential level of the Ca spike was 250 ng/ml. Addition of tetraethyl ammonium (TEA) to extracellular fluid enhanced the Ca spike in untreated cells. In toxin-treated cells, TEA did not alter the effect of tetanus toxin on the Ca spike. Blockade of the Ca spike by tetanus toxin could be detected even at low extracellular Ca2+ concentration (10 mM) by adding TEA to the extracellular fluid and adjusting the membrane potential to a steady hyperpolarized level (-80 mV) to ensure optimal and uniform electrical responses. The usefulness of NG108-15 hybrid cells for in vitro investigations on the mechanism of action of tetanus toxin was discussed.     

Voltage-activated currents in guinea pig pancreatic alpha 2 cells. Evidence for Ca2+-dependent action potentials

Glucagon-secreting alpha 2 cells were isolated from guinea pig pancreatic islets and used for electrophysiological studies of voltage- activated ionic conductances using the patch-clamp technique. The alpha 2 cells differed from beta cells in producing action potentials in the absence of glucose. The frequency of these potentials increased after addition of 10 mM arginine but remained unaffected in the presence of 5- 20 mM glucose. When studying the conductances underlying the action potentials, we identified a delayed rectifying K+ current, an Na+ current, and a Ca2+ current. The K+ current activated above -20 mV and then increased with the applied voltage. The Na+ current developed at potentials above -50 mV and reached a maximal peak amplitude of 550 pA during depolarizing pulses to -15 mV. The Na+ current inactivated rapidly (tau h approximately 0.7 ms at 0 mV). Half-maximal steady state inactivation was attained at -58 mV, and currents could no longer be elicited after conditioning pulses to potentials above -40 mV. The Ca2+ current first became detectable at -50 mV and reached a maximal amplitude of 90 pA (in extracellular [Ca2+] = 2.6 mM) at about -10 mV. Unlike the Na+ current, it inactivated little or not at all. Membrane potential measurements demonstrated that both the Ca2+ and Na+ currents contribute to the generation of the action potential. Whereas there was an absolute requirement of extracellular Ca2+ for action potentials to be elicited at all, suppression of the much larger Na+ current only reduced the upstroke velocity of the spikes. It is suggested that this behavior reflects the participation of a low-threshold Ca2+ conductance in the pacemaking of alpha 2 cells.     

The ionic requirements for the initiation of action potentials in insect muscle fibers

Electrical properties of locust leg muscle fibers were studied by means of intracellular electrodes. In most fibers, a depolarizing current pulse initiated a local response. A delayed decrease in membrane resistance appeared with more than about 10 mv depolarization. In some fibers a regenerative response also was found. Membrane constants were measured, applying the short cable model. The value of the space constant λ was 1.6 mm and the calculated value of R_m was about 1750 ohm cm². Action potentials could be elicited when the bathing fluid contained more than 2–5 mM Ba or Sr. Similar responses were seen with 2 mM Ca in the presence of tetraethylammonium (TEA). The overshoot of these action potentials increased with increasing [Ca⁺⁺]_o, [Sr⁺⁺]_o, or [Ba⁺⁺]_o, the increment for a 10-fold increase being about 29 mv for Ca and Sr and between 40 and 50 mv for Ba. These action potentials were inhibited by Mn ions but were not affected by tetrodotoxin or procaine. In solutions containing Ba or Sr, action potentials generated were suppressed by addition of Ca. The removal of Na ions did not change the configuration of the action potential. The results suggest that an increase in permeability to Ca, Ba, or Sr ions makes a major contribution to the initiation of action potentials in this tissue.     

Current recording from sensory cilia of olfactory receptor cells in situ. II. Role of mucosal Na+, K+, and Ca2+ ions

Action potential-driven current transients were recorded from sensory cilia and used to monitor the spike frequency generated by olfactory receptor neurons, which were maintained in their natural position in the sensory epithelium. Both basal and messenger-induced activities, as elicited with forskolin or cyclic nucleotides, were dependent on the presence of mucosal Na+. The spike rate decreased to approximately 20% when mucosal Na+ was lowered from 120 to 60 mM (replaced by N-methyl-D-glucamine+), without clear changes in amplitude and duration of the recorded action potential-driven transients. Mucosal Ca2+ and Mg2+ blocked spike discharge completely when increased from 1 to 10 mM in Ringer solution. Lowering mucosal Ca2+ below 1 mM increased the spike rate. These results can be explained by the presence of a cyclic nucleotide-dependent, Ca(2+)-sensitive cation conductance, which allows a depolarizing Na+ inward current to flow through the apical membrane of in situ receptor cells. A conductance with these properties, thought to provide the receptor current, was first described for isolated olfactory cells by Nakamura and Gold (1987. Nature (Lond.). 325:442-444). The forskolin-stimulated spike rate decreased when l-cis-diltiazem, a known blocker of the cyclic nucleotide-dependent receptor current, was added to the mucosal solution. Spike rate also decreased when the mucosal K+ concentration was lowered. Mucosal Ba2+ and 4-aminopyridine, presumably by means of cell depolarization, rapidly increased the spike rate. This suggests the presence of apical K+ channels that render the receptor cells sensitive to the K+ concentration of the olfactory mucus. With a slower time course, mucosal Ba2+ and 4-aminopyridine decreased the amplitude and caused rectification of the fast current transients (prolongation of action potentials). Abolishment of the apical Na+ current (by removal of mucosal Na+), as indicated by a strong decrease in spike rate, could be counteracted by adding 10 mM Ba2+ or 1 mM 4-aminopyridine to the mucosal solution, which re-established spiking. Similarly, blockage of the apical cation conductance with 10 mM Ca could be counteracted by adding 10 mM Ba2+ or by raising the mucosal K+ concentration. Thus mucosal concentrations of Na+, K+, and Ca2+ will jointly affect the sensitivity of odor detection.     

A slowly inactivating calcium current works as a calcium sensor in calcitonin-secreting cells.

Calcitonin (CT)-secreting cells (C-cells) are remarkably sensitive to changes in the extracellular Ca2+ concentration. In order to detect the mechanism by which C-cells monitor Ca2+, we compared a C-cell line responding to Ca2+ (rMTC cells) with another one known to have a defect in this Ca2+ signal transduction (TT cells). Rises of the Ca2+ concentration caused rMTC cells to depolarize and/or elicited spontaneous action potentials. Under voltage-clamp conditions, rMTC cells showed a slowly decaying Ca2+ inward current which was sensitive to dihydropyridines but not to Ni2+ at a low concentration. In contrast, the 'defective' TT cells neither depolarized nor fired action potentials with high Ca2+; they only exhibited an Ni2(+)-sensitive, transient Ca2+ current. The data strongly suggest that the slowly inactivating Ca2+ current is a prerequisite for Ca2(+)-sensitivity of C-cells and that fast inactivating channels are not sufficient to act as sensors of the extracellular Ca2+ concentration.     

Inhibition of Ca2+-activated K+ channels in pig pancreatic acinar cells by Ba2+, Ca2+, quinine and quinidine

Patch-clamp whole-cell and single-channel current recordings were made from pig pancreatic acinar cells to test the effects of quinine, quinidine, Ba2+ and Ca2+. Voltage-clamp current recordings from single isolated cells showed that high external concentrations of Ba2+ or Ca2+ (88 mM) abolished the outward K+ currents normally associated with depolarizing voltage steps. Lower concentrations of Ca2+ only had small inhibitory effects whereas 11 mM Ba2+ almost blocked the K+ current. 5.5 mM Ba2+ reduced the outward K+ current to less than 30% of the control value. Both external quinine and quinidine (200-500 microM) markedly reduced whole-cell outward K+ currents. In single-channel current studies it was shown that external Ba2+ (1-5 mM) markedly reduced the probability of opening of high-conductance Ca2+ and voltage-activated K+ channels whereas internal Ba2+ (6 X 10(-6) to 3 X 10(-5) M) caused activation at negative membrane potentials and inhibition at positive potentials. Quinidine (200-400 microM) evoked rapid chopping of single K+ channel openings acting both from the outside and inside of the membrane and in this way markedly reduced the total current passing through the channels.     

cAMP suppresses CA2+-dependent electrical activity of airway smooth muscle induced by TEA

Using intracellular microelectrodes, we investigated whether exogenous dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) or forskolin influenced the electrical effects of tetraethylammonium (TEA) on canine tracheal smooth muscle. We found that 20 mM TEA depolarized airway smooth muscle cells from a resting membrane potential (Em) of -59 +/- 4 mV (mean +/- SD) to -45 +/- 2 mV and caused spontaneous action potentials (AP's) to develop, which were 33 +/- 2 mV in amplitude. These were totally abolished in 0 Ca2+ solution. DBcAMP (1 mM) suppressed the development of this TEA-induced electrical activity and the phasic contractions electrically coupled to it. DBcAMP had no significant effect on Em in the absence of TEA however. Forskolin (1 microM) produced similar effects. Our findings suggest that Ca2+ is the principal ion responsible for the inward current associated with the TEA-induced AP's in airway smooth muscle, and that adenosine 3',5'-cyclic monophosphate may suppress the electrogenesis of this current.     

Effects of thioridazine on mechanical responses of human vas deferens induced by noradrenaline or potassium.

Thioridazine (0.1-10 mumol l-1) inhibited shortening of specimens of human vasa deferentia induced by noradrenaline (100 mumol l-1) or high extracellular potassium (136 mmol l-1). Thioridazine did not inhibit the lengthening response. In Ca(2+)-free media with EGTA (0.5 mmol l-1) similar results were obtained with responses to noradrenaline, but exposure to potassium elicited small contractions that were potentiated by thioridazine. Both shortening and lengthening responses to noradrenaline were antagonized by the alpha-adrenoceptor blockers prazosin (1-10 mumol l-1) and phentolamine (1-10 mumol l-1) and by the Ca2+ antagonists verapamil (10 mumol l-1) and diltiazem (10 mumol l-1). Responses to potassium were virtually abolished by the Ca2+ antagonists. These results show that thioridazine specifically inhibits longitudinal muscle of the human vas deferens and that its action cannot be entirely accounted for by a blockade of voltage-gated Ca2+ channels.     

Evidence that a Ca2+ sparks/STOCs coupling mechanism is responsible for the inhibitory effect of caffeine on electro-mechanical coupling in guinea pig ureteric smooth muscle

Recent studies have highlighted the role of the sarcoplasmic reticulum (SR) in controlling excitability, Ca2+ signalling and contractility in smooth muscle. Caffeine, an agonist of ryanodine receptors (RyRs) on the SR has been previously shown to effect Ca2+ signalling but its effects on excitability and contractility are not so clear. We have studied the effects of low concentration of caffeine (1 mM) on Ca2+ signalling, action potential and contractility of guinea pig ureteric smooth muscle. Caffeine produced reversible inhibition of the action potentials, Ca2+ transients and phasic contractions evoked by electrical stimulation. It had no effect on the inward Ca2+ current or Ca2+ transient but increased the amplitude and the frequency of spontaneous transient outward currents (STOCs) in voltage clamped ureteric myocytes, suggesting Ca2+-activated K+ channels (BK) are affected by it. In isolated cells and cells in situ caffeine produced an increase in the frequency and the amplitude of Ca2+ sparks as well the number of spark discharging sites per cell. Inhibition of Ca2+ sparks by ryanodine (50 microM) or SR Ca2+-ATPase (SERCA) cyclopiazonic acid (CPA, 20 microM) or BKCa channels by iberiotoxin (200 nM) or TEA (1 mM), fully reversed the inhibitory effect of caffeine on Ca2+ transients and force evoked by electrical field stimulation (EFS). These data suggest that the inhibitory effect of caffeine on the action potential, Ca2+ transients and force in ureteric smooth muscle is caused by activation of Ca2+ sparks/STOCs coupling mechanism.     

Acetylcholine suppresses calcium current in neurons of Aplysia californica

1. The left upper quadrant neurons L2-L6 in the abdominal ganglion of Aplysia californica were voltage clamped in order to examine effects of acetylcholine on voltage-dependent Ca and Ca-dependent K currents. 2. "Puffed" application of 10-100 microM acetylcholine reduced both the early inward and late outward phases of the current elicited by depolarizing voltage steps. An identical effect of the peptide FMRFamide was previously found to result from a suppression of the Ca and Ca-dependent K currents. 3. This effect of acetylcholine was obscured by the simultaneous activation of a previously described K current resembling the "S" current. Extracellular tetraethylammonium (TEA) and 4-aminopyridine could not be used to eliminate this current, because both compounds also appeared to block the acetylcholine receptor mediating the putative suppression of Ca and Ca-dependent K currents. 4. The acetylcholine-induced "S"-like and other K currents could, however, be reduced or eliminated by injection of TEA+ or Cs+ into the cell, replacement of extracellular Ca2+ with Ba2+, and by shifting the K+ equilibrium potential so as to null K currents at the potential used to record Ca current, revealing in each case a partial (10-40%) suppression of the Ca (or Ba) current by acetylcholine. 5. The reduction of the outward phase of depolarization-activated current was confirmed to represent suppression of the Ca-dependent K current by acetylcholine. This effect was indirect, secondary to the suppression of Ca current, since acetylcholine had no effect on Ca-dependent K current elicited by direct injection of Ca2+ into the cell. 6. Activation of the "S"-like K current and suppression of the Ca current by FMRFamide are likely to be important in its proposed role as an agent of presynaptic inhibition in Aplysia. Since acetylcholine has identical effects, it too may have such a function.     

L-type Ca2+ channels and K+ channels specifically modulate the frequency and amplitude of spontaneous Ca2+ oscillations and have distinct roles in prolactin release in GH3 cells

GH3 cells showed spontaneous rhythmic oscillations in intracellular calcium concentration ([Ca2+]i) and spontaneous prolactin release. The L-type Ca2+ channel inhibitor nimodipine reduced the frequency of Ca2+ oscillations at lower concentrations (100nM-1 microM), whereas at higher concentrations (10 microM), it completely abolished them. Ca2+ oscillations persisted following exposure to thapsigargin, indicating that inositol 1,4,5-trisphosphate-sensitive intracellular Ca2+ stores were not required for spontaneous activity. The K+ channel inhibitors Ba2+, Cs+, and tetraethylammonium (TEA) had distinct effects on different K+ currents, as well as on Ca2+ oscillations and prolactin release. Cs+ inhibited the inward rectifier K+ current (KIR) and increased the frequency of Ca2+ oscillations. TEA inhibited outward K+ currents activated at voltages above -40 mV (grouped within the category of Ca2+ and voltage-activated currents, KCa,V) and increased the amplitude of Ca2+ oscillations. Ba2+ inhibited both KIR and KCa,V and increased both the amplitude and the frequency of Ca2+ oscillations. Prolactin release was increased by Ba2+ and Cs+ but not by TEA. These results indicate that L-type Ca2+ channels and KIR channels modulate the frequency of Ca2+ oscillations and prolactin release, whereas TEA-sensitive KCa,V channels modulate the amplitude of Ca2+ oscillations without altering prolactin release. Differential regulation of these channels can produce frequency or amplitude modulation of calcium signaling that stimulates specific pituitary cell functions.     

Effects of bivalent cations on post-rest adaptation in guinea-pig heart muscle

In isolated papillary muscles of guinea-pig hearts, the inotropic effects of bivalent cations, Ca2+, Ba2+, Sr2+, and Ni2+, were investigated during post-rest adaptation in order to study their individual action on excitation-contraction coupling. Upon exposure to each cation studied, the force of contraction was transiently enhanced, whereas the steady state force was influenced differently: it increased with Ca2+, Ba2+ and Sr2+ and was depressed by Ni2+. The transmembrane action potentials (measured at 90% repolarization) were slightly prolonged by Sr2+ and even more by Ba2+, and were shortened by Ca2+ and Ni2+. After 10 min rest, the post-rest contractions consisted of a late peak (PII) that was enhanced in high Ca2+-solution an by Sr2+. Ni2+ and Ba2+ depressed PII and during adaptation to pre-rest controls an early peak of contraction (PI) prevailed. There was no simple relation between post-rest adaptation of force and the duration of action potential in the presence of the bivalent cations tested. During post-rest adaptation the two components of contraction can be separated. The results are interpreted in terms of a model of excitation-contraction coupling which derives Ca ions for contractile activation from two sources: transmembrane calcium influx and calcium release from cellular stores. From the different effects on post-rest adaptation it is concluded that the individual cations influence excitation-contraction coupling more specifically and not merely by "screening-off" the negative surface charges.