Q-type Ca2 Research Articles

Pituitary adenylate cyclase-activating polypeptide causes rapid Ca2+ release from intracellular stores and long lasting Ca2+ influx mediated by Na+ influx-dependent membrane depolarization in bovine adrenal chromaffin cells.

Pituitary adenylate cyclase-activating polypeptide (PACAP) has been reported to increase intracellular Ca2+ concentrations ([Ca2+]i) and catecholamine release in adrenal chromaffin cells. We measured [Ca2+]i with fura-2 and recorded ion currents and membrane potentials with the whole cell configuration of the patch-clamp technique to elucidate the mechanism of PACAP-induced [Ca2+]i increase in bovine adrenal chromaffin cells. PACAP caused [Ca2+]i to increase due to Ca2+ release and Ca2+ influx, and this was accompanied by membrane depolarization and inward currents. The Ca2+ release was suppressed by ryanodine, an inhibitor of caffeine-sensitive Ca2+ stores, but was unaffected by cinnarizine, an inhibitor of inositol trisphosphate-induced Ca2+ release. Ca2+ influx and inward currents were both inhibited by replacement of extracellular Na+, and Ca2+ influx was inhibited by nicardipine, an L-type Ca2+ channel blocker, or by staurosporine, a protein kinase C (PKC) inhibitor, but was unaffected by a combination of omega- conotoxin-GVIA, omega-agatoxin-IVA, and omega-conotoxin- MVIIC, blockers of N-, P-, and Q-type Ca2+ channels. Moreover, 1-oleoyl-2-acetyl-sn-glycerol, a PKC activator, induced inward currents and Ca2+ influx. These results indicate that PACAP causes both Ca2+ release, mainly from caffeine-sensitive Ca2+ stores, and Ca2+ influx via L-type Ca2+ channels activated by membrane depolarization that depends on PKC-mediated Na+ influx.

Pituitary adenylate cyclase-activating polypeptide causes rapid Ca2+ release from intracellular stores and long lasting Ca2+ influx mediated by Na+ influx-dependent membrane depolarization in bovine adrenal chromaffin cells

Pituitary adenylate cyclase-activating polypeptide (PACAP) has been reported to increase intracellular Ca2+ concentrations ([Ca2+]i) and catecholamine release in adrenal chromaffin cells. We measured [Ca2+]i with fura-2 and recorded ion currents and membrane potentials with the whole cell configuration of the patch-clamp technique to elucidate the mechanism of PACAP-induced [Ca2+]i increase in bovine adrenal chromaffin cells. PACAP caused [Ca2+]i to increase due to Ca2+ release and Ca2+ influx, and this was accompanied by membrane depolarization and inward currents. The Ca2+ release was suppressed by ryanodine, an inhibitor of caffeine-sensitive Ca2+ stores, but was unaffected by cinnarizine, an inhibitor of inositol trisphosphate-induced Ca2+ release. Ca2+ influx and inward currents were both inhibited by replacement of extracellular Na+, and Ca2+ influx was inhibited by nicardipine, an L-type Ca2+ channel blocker, or by staurosporine, a protein kinase C (PKC) inhibitor, but was unaffected by a combination of omega- conotoxin-GVIA, omega-agatoxin-IVA, and omega-conotoxin- MVIIC, blockers of N-, P-, and Q-type Ca2+ channels. Moreover, 1-oleoyl-2-acetyl-sn-glycerol, a PKC activator, induced inward currents and Ca2+ influx. These results indicate that PACAP causes both Ca2+ release, mainly from caffeine-sensitive Ca2+ stores, and Ca2+ influx via L-type Ca2+ channels activated by membrane depolarization that depends on PKC-mediated Na+ influx.

Glutamate receptors mediate dynamic regulation of nitric oxide synthase expression in cerebellar granule cells

Nitric oxide (NO) is a multifaceted messenger molecule believed to be involved in neural plasticity and development. Within the cerebellum, the NO synthesizing enzyme, NO synthase (NOS), is expressed exclusively by granule cells and stellate/basket neurons. In the adult cerebellum, levels of NOS expression can be used to define discrete clusters of granule cell populations. Differential expression of NOS by granule cells temporally coincides with the establishment of afferent innervation of granule cells. In primary cerebellar cultures that comprise a functional network of glutamatergic and GABAergic cerebellar neurons, blockade of electrical activity by tetrodotoxin induced the expression of the neuronal isoform of NOS (nNOS) in granule cells. Conversely, direct depolarization of cultured neurons with K+ completely downregulated nNOS expression. Suppression of NMDA receptor- and AMPA receptor-mediated spontaneous synaptic signaling in cultured cells resulted in a drastic upregulation of nNOS expression in granule neurons. In contrast, blockade of GABAA receptor-mediated intercellular communication did not affect nNOS expression by granule cells. Blocking N-, P-, and Q-type voltage-dependent Ca2+ channels resulted in a graded upregulation of NOS expression, whereas manipulations of the cAMP-dependent signal transduction pathway induced no changes. We conclude that nNOS expression in developing cerebellar granule cells is regulated by excitatory neurotransmission and that calcium is an important signal transduction molecule involved in this regulatory process.

Selective inhibition of high voltage-activated L-type and Q-type Ca2+ currents by serotonin in rat melanotrophs.

1. Whole-cell Ca2+ currents (ICa) from cultured rat melanotrophs were identified by their sensitivity to Ca2+ channel blockers, and their modulation by serotonin (5-HT) was studied. All cells displayed high voltage-activated (HVA; > -30 mV) Ca2+ currents. A low voltage-activated (LVA; > -60 mV) Ca2+ current was detected in 92% of the cells. 2. The whole-cell ICa was insensitive to omega-conotoxin GVIA (0.5-1 microM) indicating the absence of N-type Ca2+ channels. 3. At a holding potential (Vh) of -70 mV, the L-type channel blocker nifedipine reduced ICa in a dose-dependent manner with a half-maximal effective concentration (IC50) of 28 nM. The L-type current represented 39% of the total ICa. 4. omega-Agatoxin IVA (omega-Aga IVA) produced a biphasic dose-dependent inhibition of ICa, with IC50 values of 0.4 and 91 nM, indicating the presence of P-type and Q-type Ca2+ channels, which accounted respectively for 16 and 45% of the total ICa. The P-type current was also blocked by synthetic funnel-web spider toxin (sFTX 3.3; 1-10 microM) and was present only in a subpopulation (60-70%) of cells. 5. All cells possessed a Ca2+ current which was resistant to nifedipine (10 microM) and omega-Aga IVA (50 nM). This current was not affected by Ni2+ (40 microM) but was abolished by a low concentration of Cd2+ (10 microM) and by omega-conotoxin MVIIC (1 microM) indicating that it was a Q-type Ca2+ current. 6. 5-HT (10 microM) inhibited the whole-cell ICa in 70% of the cells tested (n = 120) by activating 5-HT1A and 5-HT2C receptors. 5-HT produced either a kinetic slowing of the activation phase (37% of the cells) or a scaling down (14% of the cells) of ICa. In the majority of cells (49%) both types of inhibition were found to coexist. 7. The effects of 5-HT were voltage dependent, rendered irreversible when GTP-gamma-S (30 microM) was present in the pipette solution and abolished by pretreatment of the cells with pertussis toxin (PTX; 150 ng ml-1, 18 h). 8. Low concentrations of omega-Aga IVA (20 nM), which blocked mainly P-type channels, did not reduce the effect of 5-HT on ICa. The scaling down effect of 5-HT on ICa was eliminated in the presence of nifedipine (10 microM) and the kinetic slowing effect of 5-HT persisted after blockade of L- and P-type channels but was abolished by omega-conotoxin MVIIC (1 microM). 9. We conclude that rat melanotrophs possess functional L-, P- and Q-type Ca2+ channels and that 5-HT inhibits selectively L-type and Q-type Ca2+ currents with different modalities. These effects are voltage dependent and mediated by a PTX-sensitive G-protein.

Isoproterenol potentiates synaptic transmission primarily by enhancing presynaptic calcium influx via P- and/or Q-type calcium channels in the rat amygdala

The effects of selective beta-adrenergic receptor agonist isoproterenol (Iso) on neuronal excitability and synaptic transmission were investigated in brain slices of rat amygdala. Iso (15 microM) produced a long-lasting enhancement of the EPSP that was not blocked by pretreatment with 20 microM D-2-amino-5-phosphonovalerate (D-APV) alone or D-APV in combination with kynuretic acid (1 mM). The sensitivity of postsynaptic neurons to the glutamate receptor agonist AMPA was unchanged by Iso pretreatment. Superfusion of Iso reversibly blocked the after-hyperpolarization (AHP) that followed a depolarizing current pulse and caused more action potential firing. Intracellular application of a selective inhibitor of the catalytic subunit of cAMP-dependent protein kinase A blocked the effect of Iso on the AHP, whereas Iso-induced potentiation was entirely normal in the same neuron. In addition, Iso decreased the magnitude of paired-pulse facilitation, which is consistent with a presynaptic mode of action. Substituting the Mg2+ for Ca2+ in the medium completely abolished the Iso-induced enhancement of the EPSP. The effect of Iso also was blocked by low concentrations of omega-agatoxin-IVA, but not by nifedipine or omega-conotoxin-GVIA. These results suggest that Iso enhances synaptic transmission in the amygdala via a presynaptic site of action: the mechanism underlying the potentiating effect likely is attributable to an increased Ca2+ influx through P- and/or Q-type Ca2+ channels.

Blockade of N- and Q-type Ca 2+ channels inhibit K +-evoked [ 3H]acetylcholine release in rat hippocampal slices

In the present study, we examined the contribution of specific Ca 2+ channels to K +-evoked hippocampal acetylcholine (ACh) release using [ 3H]choline loaded hippocampal slices. [ 3H]ACh release was Ca 2+-dependent, blocked by the nonspecific Ca 2+ channel blocker verapamil, but not by blockade of L-type Ca 2+ channels. The N-type Ca 2+ channel blocker, ω-conotoxin GVIA (ω-CgTx GVIA; 250 nM) inhibited [ 3H]ACh release by 44% and the P/Q-type Ca 2+ channel blocker ω-agatoxin IVA (ω-Aga IVA; 400 nM) inhibited [ 3H]ACh release by 27%, with the combination resulting in a nearly additive 79% inhibition. Four hundred or one thousand nM ω-Aga IVa was necessary to inhibit [ 3H]ACh release, ω-Conotoxin MVIIC (ω-CTx-MVIIC) was used after first blocking N-type Ca 2+ channels with ω-CgTx GVIA (1 μM). Under these conditions, 500 nM ω-CTx-MVIIC led to a nearly maximal inhibition of the ω-CgTx GVIA-insensitive [ 3H]ACh release. Based on earlier reports about the relative sensitivity of cloned and native Ca 2+ channels to these toxins, this study indicates that N- and Q-type Ca 2+ channels primarily mediate K +-evoked hippocampal [ 3H]ACh release.

Serotonin modulates high-voltage-activated CA 2+ channels in rat ventromedial hypothalamic neurons

The modulation of high-voltage-activated (HVA) Ca 2+ channels by serotonin (5-HT) was studied in ventromedial hypothalamic (VMH) neurons acutely dissociated from 12–14-day-old Wistar rats using the whole-cell and nystatin perforated-patch recording configurations. 5-HT inhibited the HVA Ca 2+ channels in a concentration-, time- and voltage-dependent manner. This inhibition was mimicked by the 5-HT 1A agonist 8-hydroxy-dipropylaminotetralin and was prevented by pretreatment with pertussis toxin (PTX). ω-Conotoxin-GVIA, ω-agatoxin-IVA, nicardipine and ω-conotoxin-MVIIC blocked each fraction of HVA Ca 2+ channel currents, suggesting the existence of N-, P-, L- and Q-types of HVA Ca 2+ channels. A component of the current resistant to these Ca 2+ channel antagonists also existed in the VMH neurons. Among these five components of HVA Ca 2+ channel currents, the N- and Q-type currents were significantly inhibited by 5-HT. These findings suggest that the activation of 5-HT 1A receptors produces the selective inhibition of N- and Q-type Ca 2+ channels through a PTX-sensitive G-protein in rat VMH neurons.

Functional impact of syntaxin on gating of N-type and Q-type calcium channels.

Rapid and reliable synaptic transmission depends upon the close proximity of voltage-gated calcium channels and neurotransmitter-containing vesicles in the presynaptic terminal. Although it is clear that a local Ca2+ rise conveys the crucial signal from Ca2+ channels to the exocytotic mechanism, little is known about whether communication ever proceeds in the opposite direction, from the release machinery to Ca2+ channels. To look for such signalling, we examined the interaction of various types of voltage-gated Ca2+ channels with syntaxin, a presynaptic membrane protein of relative molecular mass 35,000 which may play a key part in synaptic vesicle docking and fusion and which interacts strongly with N-type Ca2+ channels. Here we report that co-expression of syntaxin 1A with N-type channels in Xenopus oocytes sharply decreases the availability of these channels. This is due to the stabilization of channel inactivation rather than to a simple block or lack of channel expression, because it is overcome by strong hyperpolarization. Deletion of syntaxin's carboxy-terminal transmembrane domain abolishes its functional effect on Ca2+ channels. Syntaxin produced a similar effect on Q-type Ca2+ channels encoded by alpha 1A but not on L-type Ca2+ channels. Thus, the syntaxin effect is specific for Ca2+ channel types that participate in fast transmitter release in the mammalian central nervous system. We hypothesize that, in addition to acting as a vesicle-docking site, syntaxin may influence presynaptic Ca2+ channels, opposing Ca2+ entry where it is not advantageous, but allowing it at release sites where synaptic vesicles have become docked and/or ready for fusion.

Complete and reversible block by ω-grammotoxin SIA of glutamatergic synaptic transmission between cultured rat hippocampal neurons

ω-Grammotoxin SIA (ω-GsTx SIA), a peptide isolated from tarantula venom, inhibits synaptosomal Ca 2+ influx and neurotransmitter release, and blocks N-, P-, and Q-type voltage-gated Ca 2+ channels. The whole-cell patch-clamp was used to record glutamatergic excitatory post-synaptic currents (EPSCs) evoked by extracellular stimulation of presynaptic neurons in primary rat hippocampal cultures. EPSCs displayed rapid kinetics and were blocked by CNQX. ω-Conotoxin (1 μM) GVIA inhibited EPSCs by 46%, while 30 nM and 1 μM ω-agatoxin IVA produced 12% and 69% inhibition, respectively, consistent with coupling of N-, P- and Q-type Ca 2+ channels to glutamatergic synaptic transmission. ω-GsTx SIA (1 μM) rapidly, completely, and reversibly blocked glutamatergic EPSCs, but did not affect currents evoked by bath application of kainate. Thus, ω-GsTx SIA blocks glutamatergic synaptic transmission by blocking presynaptic voltage-gated Ca 2+ channels. ω-GsTx SIA is the only agent that blocks selectively and reversibly the Ca 2+ channels coupled to glutamate release. ω-GsTx SIA provides a unique and powerful tool for experiments requiring recovery of function following presynaptic block of synaptic transmission.

Diversity of voltage-gated calcium currents in large diameter embryonic mouse sensory neurons.

Voltage-gated Ca2+ currents were investigated in a subpopulation of dorsal root ganglion neurons (large diameter, neurofilament-positive) acutely isolated from 13-day-old mouse embryos and recorded using the whole-cell patch-clamp technique. Low- and high-voltage-activated calcium currents were recorded. These currents could be identified and separated by their distinct (i) threshold of activation, (ii) ability to run-up during the early phase of recording and (iii) decay kinetics using Ba2+ instead of Ca2+ as the charge carrier. Among high-voltage-activated currents, L-, N- and P-type Ca2+ currents were identified by their sensitivity to, respectively, the dihydropyridine agonist Bay K 8644 (5 microM) and antagonist nitrendipine (3 microM), omega-conotoxin GVIA (3 microM) and omega-agatoxin IVA (30 nM). In the combined presence of nitrendipine (3 microM), omega-conotoxin GVIA (3 microM) and omega-agatoxin IVA (30 nM), two additional high-voltage-activated components were detected. One, blocked by 500 nM omega-conotoxin MVIIC and 1 microM omega-agatoxin IVA, had properties similar to those of the Q-type Ca2+ current first reported in cerebellar granule cells. The other, defined by its resistance to saturating concentrations of all the blockers mentioned above applied in combination, resembles the R-type Ca2+ current also described in cerebellar granule cells. In conclusion, embryonic sensory neurons appear to express a large repertoire of voltage-activated Ca2+ currents with distinct pharmacological properties. This diversity suggests a great variety of pathways for Ca2+ signaling which may support different functions during development.

Somatostatin modulates high-voltage-activated Ca2+ channels in freshly dissociated rat hippocampal neurons

1. The effects of somatostatin (SS) on the low-voltage-activated and high-voltage-activated (HVA) Ca2+ channels in pyramidal neurons acutely dissociated from the hippocampal CA1 region of 2- to 3-wk-old rats were investigated in a nystatin perforated-patch recording configuration under voltage-clamp conditions. 2. SS had no effect on the low-voltage-activated Ca2+ channel but did inhibit the HVA Ca2+ channel in a concentration-, time-, and voltage-dependent manner. 3. SS showed the activation phase of Ba2+ current (IBa) passing through HVA Ca2+ channels, and the maximum inhibition was 28% of the total current amplitude measured 10 ms after the current activation. The inhibitory effect was eliminated by applying larger depolarizing prepulses. Pretreatment with pertussis toxin (PTX) completely blocked the effect of SS on HVA IBa, suggesting the contribution of PTX-sensitive Gi/Go proteins to the SS-induced inhibition. 4. The applications of forskolin, 8-Br-cAMP, dibutyryl-guanosine 3'5'-cyclic monophosphate, staurosporine, and 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine did not affect either the control HVA IBa or the SS-induced inhibition of HVA IBa. 5. Pretreatment with protein kinase C (PKC) activators had no significant effect on HVA IBa but did remove the inhibition of HVA IBa by SS. 6. Omega-Conotoxin-GVIA, omega-agatoxin-IVA, nicardipine, and omega-conotoxin-MVIIC blocked HVA IBa by 27, 13, 38, and 9% of the total HVA current, respectively, which suggested the existence of N-, P-, L-, and Q-type HVA Ca2+ channels in the hippocampal CA1 pyramidal neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Modulation of calcium channels by metabotropic glutamate receptors in cerebellar granule cells

We investigated the mechanisms by which metabotropic glutamate receptors (mGluRs) modulate specific Ca 2+ channels in cerebellar granule cells. A large fraction of the current in granule cells is carried by L- and Q-type Ca 2+ channels (about 26% each), whereas N- and P-type contribute proportionally less to the global current (9 and 15%, respectively). 1-Aminocyclopentane-dicarboxylate ( t-ACPD), (2 S,3 S,4 S)- α-(carboxycyclopropyl)-glycine ( l-CCGI) and ( S)-4-carboxy-3-hydroxyphenylglycine [( S)-4C3HPG], but not l( + )-2-amino-4-phosphonobutyrate ( l-AP4) reduced the Ca 2+ current amplitude. The t-ACPD-induced inhibition was fully antagonized by ( ± )-methyl-4-carboxyphenylglycine [( ± )-MCPG] and blocked by pertussis toxin (PTX). These results are consistent with inhibitory response mediated by mGluR2/R3. The use of specific Ca 2+ channel blockers provided evidence that mGluR2/R3 inhibited both L- and N-type Ca 2+ currents. In PTX-treated cells, Glu or t-ACPD, but not l-CCGI or l-AP4, increased the Ca 2+ current. Consistent with the activation of mGluR1, the antagonists ( + )-MCPG and ( S)-4C3HPG prevented the facilitation of Ca 2+ current produced by t-ACPD. The mGluR1-activated facilitation was completely blocked by nimodipine, indicating that L-type Ca 2+ currents were selectively potentiated.

Effects of Ca2+ channel blockers on directional selectivity of rabbit retinal ganglion cells

1. Extracellular recordings were made from ON-OFF directionally selective ganglion cells in superfused rabbit retinas in order to examine the effects of voltage-activated Ca2+ channel blockers on the response of these ganglion cells to a moving bar of light. 2. Bath application of Cd2+ (67-110 microM) abolished directional selectivity in the ganglion cells. That is, the cells gave nearly equal responses to the leading and trailing edges of a bar of light moved in the preferred and null directions. This effect of Cd2+ was rapidly reversible. 3. Directional selectivity in the ganglion cells was not affected by Ni2+ (120-440 microM), Co2+ (180-690 microM), or the L-type Ca2+ channel blockers nicardipine (7-29 microM) and methoxyverapamil (18-60 microM). These blockers did, however, reduce the responses of the ganglion cells to a bar of light moved in the preferred direction. 4. omega-Conotoxin MVIIC (130 nM-1.9 microM), which potently blocks N-type and Q-type Ca2+ channels, abolished directional selectivity in the ganglion cells. omega-Conotoxin MVIIC not only brought out large leading and trailing edge responses to movement of a bar of light in the null direction, but it also increased the leading and trailing edge responses to movement of the bar of light in the preferred direction. The effect of omega-conotoxin MVIIC was slowly reversible. 5. The N-type Ca2+ channel blocker omega-conotoxin GVIA (1.4-6.3 microM) did not abolish directional selectivity in the ganglion cells. This blocker did, however, bring out some response to the leading edge of a bar of a light moved in the null direction. This effect of omega-conotoxin GVIA appeared to be irreversible. 6. omega-Agatoxin IVA, a potent blocker of P-type Ca2+ channels, when bath applied at low concentrations (66-83 nM), increased the responses to movement of a bar of light in the preferred direction but brought out only small responses to movement of the bar of light in the null direction. At high concentrations (250-280 nM) that reportedly block Q-type Ca2+ channels by > or = 50%, omega-agatoxin IVA nearly abolished directional selectivity. This effect of omega-agatoxin IVA was slowly reversible. 7. These results indicate that omega-conotoxin MVIIC- and omega-agatoxin IVA-sensitive Ca2+ channels (possibly Q-type channels) play an important role in the generation of directional selectivity in rabbit retinal ganglion cells.

Developmental changes in presynaptic calcium channels coupled to glutamate release in cultured rat hippocampal neurons

Excitatory synaptic transmission in the hippocampus involves the participation of at least two types of presynaptic Ca2+ channels, N-type channels sensitive to omega-conotoxin GVIA (omega-CTx GVIA) and Q-type channels sensitive to omega-agatoxin IVA (omega-Aga IVA). Hippocampal pyramidal neurons in cell culture were used to examine the participation of these two classes of channels at different stages of synapse development. Specific Ca2+ channel toxins were used to block presynaptic Ca2+ channels while whole-cell voltage-clamp recordings were used to record evoked EPSCs in postsynaptic neurons. At immature synapses (cells in culture for 10-15 d), omega-CTx GVIA (1-5 microM) blocked transmission by more than 80% while omega-Aga IVA (1 microM) was less effective. In older cultures, however, omega-Aga IVA (1 microM) was more effective than omega-CTx GVIA (1-5 microM) in blocking synaptic transmission. The pharmacological properties of the omega-Aga IVA sensitive component of synaptic transmission were examined in more detail using omega-Aga IVA and omega-conotoxin MVIIC (omega-CTx MVIIC). The properties of this component of transmitter release indicated that a Q-type Ca2+ channel was involved in presynaptic Ca2+ entry. The results suggest that different classes of presynaptic Ca2+ channels begin to participate in transmitter release at different times during synapse development and maturation.

Solution Structure of ω-Conotoxin MVIIC Determinined by NMR

The solution structure of the P- and Q-type Ca 2+ channel blocker, ω-conotoxin MVIIC (a peptidic neurotoxin composed of 26 amino acid residues),has been determined by 1H-NMR and simulated annealing calculations. The resulting calculated structures converged very well to a conformation with an average value of pairwised RMSD for N, Cα and C′ of 0.62 Å. Lys-25 is buried in the molecule and less flexible so that among the four Lys residues, its side chain provides the lowest reactivity on biotinylation and the mono-biotinylation in this residue less influences the biological activity.

オピオイドレセプターの情報伝達系による脱感作の違い

RNA-injected Xenopus oocytes were used for studying homologous desensitization of opioid receptors to G-protein-coupled intracellular signaling pathways. In the oocytes expressing K opioid receptor, voltage-dependent Ca2+ channel α2+ and β subunits, the κ agonist U50488H (1 μM) inhibited Ca2+ channel current in a reversible manner, and the inhibition was diminished by sustained agonist exposure (homologous desensitization). More than 10 min was required to halve the inhibition of BI- or Q-type Ca2+ channels by the κ agonist, however, the t½ for U50488H-induced inhibition of BIII- or N-type channels was only 6±1 min. Moreover, in the oocytes expressing κ opioid receptor, EP4 prostaglandin receptor and CFTR channel, no apparent desensitization was observed in the κ receptor-mediated potentiation of the cyclic AMP production by prostaglandin E2 even when the oocytes were treated with U50488H for 2 hours or more. The time-course of desensitization of μ opioid receptor was also different in the effector molecules. These observations suggest that rate of homologous desensitization of opioid receptor is not only dependent on the receptor molecule itself but also on its intracellular signaling systems.

Roles of N-Type and Q-Type Ca 2+ Channels in Supporting Hippocampal Synaptic Transmission

Several types of calcium channels found in the central nervous system are possible participants in triggering neurotransmitter release. Synaptic transmission between hippocampal CA3 and CA1 neurons was mediated by N-type calcium channels, together with calcium channels whose pharmacology differs from that of L- and P-type channels but resembles that of the Q-type channel encoded by the alpha 1A subunit gene. Blockade of either population of channels strongly increased enhancement of synaptic transmission with repetitive stimuli. Even after complete blockade of N-type channels, transmission was strongly modulated by stimulation of neurotransmitter receptors or protein kinase C. These findings suggest a role for alpha 1A subunits in synaptic transmission and support the idea that neurotransmitter release may depend on multiple types of calcium channels under physiological conditions.

Central effects of oxytocin

Article de synthese sur les effets centraux de l'ocytocine chez les mammiferes: effets physiologiques et comportementaux; site cerebral et mecanisme d'action de l'ocytocine; sites de liaisons de l'ocytocine dans le cerveau et relation avec son activite biologique