Radiologic aspects of COVID-19 pneumonia: outcomes and thoracic complications. / Aspectos radiológicos de la neumonía COVID-19: evolución y complicaciones torácicas.

Outcomes vary widely in patients with COVID-19. Whereas some patients have only mild symptoms of short duration, others develop severe disease that leads to acute respiratory distress syndrome requiring prolonged stays in intensive care units. Radiologically, the initial stage is characterized by viral pneumonia with mild expression. In some patients, however, the onset of the immune response results in acute lung damage with organizing pneumonia and diffuse alveolar damage. Moderate-severe disease is associated with a high incidence of pulmonary embolisms, generally peripherally distributed and associated with endothelial damage, prolonged stays in bed, and coagulopathy. Other relatively common complications are spontaneous pneumothorax and pneumomediastinum due to the rupture of alveolar walls and barotrauma in mechanically ventilated patients. Superinfection, generally bacterial and less commonly fungal, is more common in patients with severe disease.

Aspectos radiológicos de la neumonía COVID-19: evolución y complicaciones torácicas / Radiologic aspects of COVID-19 pneumonia: outcomes and thoracic complications

Los pacientes con COVID-19 presentan una evolución muy variable: desde enfermos con síntomas leves de corta duración a pacientes con enfermedad grave que desarrollan un síndrome de distrés respiratorio agudo, con ingresos prolongados en unidades de críticos. Desde el punto de vista radiológico, la etapa inicial se caracteriza por una neumonía viral poco expresiva. No obstante, en algunos pacientes, con el inicio de la respuesta inmunitaria se produce un daño pulmonar agudo con patrones radiológicos de neumonía organizada y daño alveolar difuso. La enfermedad moderada-grave se asocia con una incidencia alta de tromboembolismo pulmonar, generalmente de distribución periférica y asociado al daño endotelial, encamamiento prolongado y coagulopatía de la enfermedad. Otras complicaciones relativamente frecuentes son: el neumotórax y el neumomediastino espontáneos por rotura de paredes alveolares, y el barotrauma en pacientes con ventilación mecánica. La sobreinfección es más frecuente en pacientes graves, generalmente de origen bacteriano y menos frecuente fúngico

Outcomes vary widely in patients with COVID-19. Whereas some patients have only mild symptoms of short duration, others develop severe disease that leads to acute respiratory distress syndrome requiring prolonged stays in intensive care units. Radiologically, the initial stage is characterized by viral pneumonia with mild expression. In some patients, however, the onset of the immune response results in acute lung damage with organizing pneumonia and diffuse alveolar damage. Moderate-severe disease is associated with a high incidence of pulmonary embolisms, generally peripherally distributed and associated with endothelial damage, prolonged stays in bed, and coagulopathy. Other relatively common complications are spontaneous pneumothorax and pneumomediastinum due to the rupture of alveolar walls and barotrauma in mechanically ventilated patients. Superinfection, generally bacterial and less commonly fungal, is more common in patients with severe disease

Neutrophil-to-lymphocyte ratio and mesenteric ischemia: can it predict the etiology of mesenteric ischemic at computed tomography?

OBJECTIVES: To assess the usefulness of the neutrophil-to-lymphocyte ratio (NLR) as a predictive factor of acute mesenteric ischemia (AMI) in patients presenting at the emergency department (ED) with acute abdominal pain. METHODS: This is a retrospective case-control study of patients older than 16 years admitted to the ED with acute abdominal pain with CT and histologic confirmation. The study group corresponded to patients with abdominal CT with radiological signs of AMI. The control group corresponded to patients with non-AMI findings in abdominal CT. Association measurements of NLR with radiological signs were compared with a paired-sample t test, and multivariate regression performed to analyze potential correlations. To assess the diagnosis capacity of NLR, ROC curves were calculated. RESULTS: A total of 61 patients were included (32 cases and 29 controls). The cases of AMI showed higher mortality (43.8% vs 6.9%, p < 0.01) and higher NLR on the limit of statistical significance (13.8 vs 8.7, p = 0.053). Patients with AMI due to occlusion of the superior mesenteric artery (SMA) showed a higher NLR (8.3 vs 22.3, p < 0.001). The area under the curve (AUC) of the NLR for AMI due to occlusion of the SMA was 0.88 (95% CI 0.7-1.0, p = 0.001). No patient with NLR < 5 presented AMI due to occlusion of the SMA. An NLR of 12.8 showed a sensitivity of 92% and a specificity of 74% for AMI due to occlusion of SMA. CONCLUSIONS: The NLR is a useful parameter of AMI of arterial origin due to occlusion of the SMA; it can help the clinician to raise suspicion of this diagnosis and the interpreting radiologist in the acquisition protocol for the CT study and would alert for an early surgical treatment.

[Intraparotid first branchial arch cyst: complex diagnostic and therapeutic process]. / Quiste de primer arco branquial intraparotídeo: complejo proceso diagnóstico y terapéutico.

First branchial arch cysts are uncommon. Therefore, together with its variable clinical and age presentation they are often misdiagnosed at first. The treatment is surgical, requiring a correct procedure to avoid future recurrences. In this paper we describe a typical case of first branchial arch cyst in which as described in other reports, we first made several misdiagnoses and therefore an inadequate treatment and lastly, with the correct diagnosis, we performed a meticulous complete excision under facial nerve monitoring.

Quiste de primer arco branquial intraparotídeo: complejo proceso diagnóstico y terapéutico / Intraparotid first branchial arch cyst: Complex diagnostic and therapeutic process

Los quistes branquiales del primer arco son infrecuentes. Por este motivo, unido a su clínica y edad de aparición variables, a menudo se realizan diagnósticos primarios erróneos. El tratamiento es quirúrgico, requiriéndose un correcto procedimiento para evitar futuras recidivas. En este trabajo describimos un caso típico de quiste de primer arco branquial intraparotídeo en el que, al igual que en otros casos publicados, se realizaron al principio varios diagnósticos erróneos y por tanto un tratamiento inadecuado. Finalmente, con el diagnóstico correcto se llevó a cabo una meticulosa extirpación completa bajo monitorización del nervio facial (AU)

First branchial arch cysts are uncommon. Therefore, together with its variable clinical and age presentation they are often misdiagnosed at first. The treatment is surgical, requiring a correct procedure to avoid future recurrences. In this paper we describe a typical case of first branchial arch cyst in which as described in other reports, we first made several misdiagnoses and therefore an inadequate treatment and lastly, with the correct diagnosis, we performed a meticulous complete excision under facial nerve monitoring (AU)

Specific activation of the alpha 7 nicotinic acetylcholine receptor by a quaternary analog of cocaine.

Effects of cocaine and cocaine methiodide were evaluated on the homomeric alpha 7 neuronal nicotinic receptor (nAChR). Whereas cocaine itself is a general nAChR noncompetitive antagonist, we report here the characterization of cocaine methiodide, a novel selective agonist for the alpha 7 subtype of nAChR. Data from (125)I-alpha-bungarotoxin binding assays indicate that cocaine methiodide binds to alpha 7 nAChR with a K(i) value of approximately 200 nM while electrophysiology studies indicate that the addition of a methyl group at the amine moiety of cocaine changes the drug's activity profile from inhibitor to agonist. Cocaine methiodide activates alpha 7 nAChR with an EC(50) value of approximately 50 microM and shows comparable efficacy to ACh in oocyte experiments. While agonist effects are specific for the alpha 7 neuronal nAChR and are not observed with heteromeric neuronal or skeletal muscle nAChR, antagonist effects are present for heteromeric nAChR combinations. Studies of PC12 cells transiently transfected with human alpha 7 cDNA and expressing a variety of functional nicotinic receptor subtypes confirm the specificity of cocaine methiodide agonist effects. Our results indicate that a quaternary structural derivative of cocaine can be used as a specific agonist for the alpha 7 subtype of neuronal nicotinic receptor.

Two domains of the beta subunit of neuronal nicotinic acetylcholine receptors contribute to the affinity of substance P.

Substance P is known to noncompetitively inhibit activation of muscle and neuronal nicotinic acetylcholine receptors. Neuronal nicotinic receptors formed from different combinations of alpha and beta subunits exhibited differential sensitivity to substance P, with those containing beta-4 subunits having a 25-fold higher affinity than those having beta-2 subunits. To identify the regions and/or amino acid residues of the beta subunit responsible for this difference, chimeric beta subunits were coexpressed with alpha-3 in Xenopus oocytes and the IC50 values for substance P were determined. Amino acid residues between 105 and 109 (beta4 numbering), in the middle of the N-terminal domain, and between 214 and 301, between the extracellular side of M1 and the intracellular side of M3, were identified as major contributors to the apparent affinity of substance P. The affinity of acetylcholine was only affected by residue changes between 105 and 109. Site-directed mutagenesis revealed two amino acids that are important determinants of the affinity of substance P, beta4(V108)/beta2(F106), which is in the middle of the first extracellular domain, and beta4(F255)/beta2(V253), which is within the putative channel lining transmembrane domain M2. However, other residues within these domains must be making subtle but significant contributions, since simultaneous mutation of both these amino acids did not cause complete interconversion of the beta subunit-dependent differences in the receptor affinity for substance P.

The beta subunit of neuronal nicotinic acetylcholine receptors is a determinant of the affinity for substance P inhibition.

Substance P is known to inhibit nicotinic acetylcholine receptors from neuronal tissue, skeletal muscle, and electroplaque. The interaction of substance P with specific combinations of neuronal nicotinic acetylcholine receptor subunits was studied by expressing various combinations of subunits in Xenopus oocytes. The response to acetylcholine was inhibited by substance P with all subunit combinations tested; however, the apparent affinity for substance P varied by 20-30-fold. The affinity seemed to be dependent on the beta subtype expressed (beta 4 or beta 2). This suggests that the beta subunit may contribute, at least partially, to the substance P binding site. In the case of the alpha 7 subtype, which forms a homooligomeric receptor, the apparent affinity for substance P was intermediate between those of the two beta subtypes coexpressed with either alpha 3 or alpha 4. As previously found, the inhibition was noncompetitive. Furthermore, the inhibition was not voltage dependent and, therefore, is unlikely to be due to substance P blocking the channel within the transmembrane portion of the pore.

Characterization of the binding of [3H]substance P to the nicotinic acetylcholine receptor of Torpedo electroplaque.

The binding of [3H]substance P to nicotinic acetylcholine receptor-enriched Torpedo electroplaque membranes was characterized. In the absence of cholinergic agonist, [3H]substance P binding was displaced by unlabeled substance P with an IC50 of 31 +/- 7 microM. In the presence of 10 mM carbamylcholine, displacement reflected two populations of binding sites with IC50 values of 0.93 +/- 0.39 and 30 +/- 5 microM, with the higher affinity component contributing 69 +/- 2% of the inhibition. Equilibrium binding parameters were calculated by transformation of the concentration dependences of inhibition into saturation isotherms. In the absence of agonist, substance P bound with a Kd of 42 +/- 7 microM to 3-4 sites/alpha-bungarotoxin binding site. In the presence of agonist, substance P bound to two sites, a low affinity site not significantly different from that seen in the absence of agonist (Kd = 25 +/- 8 microM, approximately 3 sites/alpha-bungarotoxin site) and a high affinity site with a Kd of 0.55 +/- 0.32 microM (approximately 1 site/2 alpha-bungarotoxin sites, 1 site/receptor). The increase in substance P binding induced by carbamylcholine was blocked by the nicotinic antagonists alpha-bungarotoxin and d-tubocurarine but was not affected by the muscarinic antagonist atropine. The concentration dependence of the carbamylcholine-induced increase had two components, with EC50 values for the agonist of 9.1 +/- 4.2 microM (56 +/- 16% of the increase) and 1.3 +/- 0.5 mM. The structural specificity of agonist-dependent high affinity substance P binding was identical to that seen for inhibition of nicotinic receptor activation and substantially different from that of binding to the G protein-coupled tachykinin receptors. From the time courses of association, it appears that substance P binds preferentially to a transient agonist-induced receptor state. The gamma and delta subunits of the receptor were specifically labeled in an agonist-dependent manner after cross-linking of [3H]substance P to the receptor with the bifunctional cross-linking reagent bis[2-(succinimidooxycarbonyloxy)ethyl]sulfone or after photoaffinity labeling of the receptor with 125I-p-benzoylphenylalanine-substance P. These results demonstrate the existence of a high affinity agonist-induced binding site for substance P on the nicotinic acetylcholine receptor that probably mediates the noncompetitive inhibition by the peptide of receptor activation.

Effects of substance P on the binding of agonists to the nicotinic acetylcholine receptor of Torpedo electroplaque.

The effect of the neuropeptide substance P on the binding of the cholinergic ligands to the nicotinic acetylcholine receptor of Torpedo electroplaque membranes was examined at a physiological concentration of NaCl (150 mM). Substance P had no effect on the initial rate of 125I-alpha-bungarotoxin binding at concentrations of < 100 microM. The peptide did not bind to the high-affinity local anesthetic site but allosterically modulated [3H]phencyclidine binding, positively in the absence of agonist and negatively in the presence of agonist. Substance P increased the apparent affinity of the cholinergic agonists carbamylcholine and acetylcholine at equilibrium. The effect of substance P on the equilibrium binding of [3H]acetylcholine was examined directly, and the peptide appeared to increase the affinity of the binding of the second molecule of agonist, with no effect on the binding of the first. This indicates that substance P can affect the cooperative interactions between agonist binding sites. Substance P appeared to increase the rate of carbamylcholine-induced desensitization; however, the data are also consistent with an allosteric mechanism that does not involve the desensitized state. To attempt to differentiate between these mechanisms, the rates of recovery were determined after exposure to peptide and/or agonist. The kinetics of recovery are consistent with stabilization of the desensitized state by substance P if the peptide remains bound long enough to allow rapid recovery to the low-affinity state. However, an allosteric modulation of agonist binding that does not involve the desensitized state cannot be ruled out.

Substance P inhibits carbamylcholine-stimulated 22Na+ efflux from acetylcholine receptor-enriched Torpedo electroplaque membrane vesicles.

The effect of substance P on nicotinic acetylcholine receptor function was examined in Torpedo electroplaque membranes. The peptide inhibited carbamylcholine-stimulated 22Na+ efflux in a concentration-dependent manner. By irreversibly blocking spare receptors with alpha-bungarotoxin, the IC50 for substance P was shown to be less than 3 microM. Inhibition by substance P was slow relative to receptor activation by carbamylcholine, consistent with an enhancement of desensitization or a slow allosteric block.

Binding of the dihydropyridine calcium channel blocker (+)-[3H] isopropyl-4-(2,1,3-benzoxadiazol-4-yl)-1,4-dihydro-5-methoxycarbonyl-2, 6-dimethyl-3-pyridinecarboxylate (PN200-110) to RINm5F membranes and cells: characterization and functional significance.

This report provides direct evidence for a dihydropyridine receptor/calcium channel in the insulin-secreting beta-cell line RINm5F. The receptor/channel can modulate the intracellular Ca++ concentration and the resultant insulin secretion by regulating the influx of extracellular Ca++ through dihydropyridine-sensitive voltage-dependent L-type Ca++ channels. Elevated extracellular K+ or the dihydropyridine Ca++ channel agonist, BAY k 8644 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethyl- phenyl)pyridine-5-carboxylate], stimulated the uptake of 45Ca++, raised [Ca++]i, and increased insulin secretion in a concentration-dependent manner. These actions were inhibited by L-type Ca++ channel blockers including nitrendipine, verapamil and diltiazem. (+)-[3H]PN200-110 bound specifically with high affinity to RINm5F cell membranes (Kd approximately 200 pM). Specific binding was inhibited competitively by dihydropyridines whereas phenylalkylamines inhibited incompletely (+)-[3H]PN200-110 binding, consistent with an allosteric interaction. The benzothiazepine diltiazem had no effect on (+)-[3H]PN200-110 binding in the presence of Ca++, but increased binding allosterically in the absence of Ca++ (in the presence of EGTA). Maximal (+)-[3H]PN200-110 binding required divalent cations, with Mg++, Mn++ and Ba++ essentially as effective as Ca++ in reversing the effects of EGTA, whereas binding was not supported by Cd++ or La . Specific high affinity (+)-[3H]PN200-110 binding was also demonstrated in intact RINm5F cells and shown to be modulated by membrane potential. Depolarization of the cells by raising extracellular K+ from 5 to 80 mM increased the affinity of (+)-[3H]PN200-110 4- to 5-fold (decreased Kd) with no significant effect on the maximum number of binding sites.

[Possibilities and limits of immunodiagnosis of strongyle infections in horses]. / Möglichkeiten und Grenzen der Immundiagnostik des Strongylidenbefalles beim Pferd.

In an investigation period over 8 months the natural course of infection was studied by means of coproscopic and serological methods in 27 mares and 29 foals. The examination of the stool showed in mares, before the beginning of the grazing season, an infection rate of 100% with small and a rate of 7.4% with large strongyles (Str. vulgaris). Serologically the ELISA showed in foals only a distinct increase of antibody activity with the somatic antigen. The mares retained the high IgG-values of activity, which were already found at the beginning of the investigations. Even though the agglutination test can be applied for control of the effectiveness of therapy in a horse population, individual diagnostic possibilities remain limited. This is due to the reduced sensitivity and specificity of the IgG(T)-concentration under natural conditions of infection. The double-antibody-sandwich-ELISA technique has shown to be basically feasible as a test for antigens from small strongyles. Somatic antigen could most sensitively be demonstrated by antibodies to ES-antigen, ES-antigen, however, by antibodies against somatic antigens.

[Leukocyte migration inhibition after experimental trypanosome infection in cattle]. / Leukozytenmigrationshemmung nach experimenteller Trypanosomeninfektion beim Rind.

Blood serum from cattle experimentally infected with trypanosomes was tested for its activity influencing granulocyte migration. Pooled porcine granulocytes were used in the migration assay. The inhibitory migration activity observed in serum samples of trypanosome infected animals implies the presence of mediators of cellular immunity. Values of migration indices express reciprocal events of inhibitory and stimulating events in infected animals. This study allowed to follow at least some aspects of the very complex cellular immune system and its functioning. The observed differences in migration values in serum of each animal speak for an individual immunological capacity to defy trypanosome infections. The variability in occurrence of the first inhibitory activity after infection supports the view of individual responsiveness. Distinct differences in migration values were observed in Dahomey cattle after primary and secondary challenge with trypanosomes. Serum from reinfected animals exhibited a marked decrease in inhibitory activity as compared to samples obtained after first infection. These observations suggest a modulation of the individual immune response after multiple challenge with trypanosomes of the same strain. This study demonstrates the involvement of cell mediated immune responses to trypanosome infections.

Two calcium channels in basolateral membranes of rabbit ileal epithelial cells.

The actions of three different types of calcium channel blockers on short-circuit current (Isc) in rabbit ileum were studied. These included the phenylalkylamines, verapamil and (l)-desmethoxyverapamil (D888); the dihydropyridines, nifedipine and nitrendipine; and the benzothiazepine, diltiazem. All of the drugs decreased Isc, a change associated with increased Na and Cl absorption. Verapamil and D888 had the largest effects. The dihydropyridine, BAY K 8644, a calcium channel activator, increased Isc and decreased Na and Cl absorption, effects not inhibited by tetrodotoxin. The phenylalkylamines had an additional effect on Isc in the presence of a maximally inhibitory concentration of the dihydropyridines, suggesting the possibility of two distinct calcium channels, one of which is the L-type voltage-activated, dihydropyridine- and phenylalkylamine-sensitive channel, and the other is a channel only sensitive to phenylalkylamines but not to dihydropyridines. [3H]nitrendipine and [3H]D888 binding to an enriched preparation of basolateral membranes from ileal epithelial cells was characterized. Each ligand bound specifically and saturably to an apparently single population of high-affinity sites with [3H]D888 having three times as many binding sites as [3H]nitrendipine. [3H]nitrendipine binding was partially inhibited by verapamil and D888 and was increased by diltiazem; whereas [3H]D888 binding was inhibited completely by verapamil but only partially by nitrendipine and diltiazem. These transport and binding studies suggest the presence of two types of Ca2+ channels in ileal epithelial cells, one of which interacts with the dihydropyridines, the phenylalkylamines, and the benzothiazepines at three different sites and the other channel that only binds the phenylalkylamines.

The significance of immunodiagnosis in schistosomiasis control: a brief review.

Various immunodiagnostic methods have been employed for the demonstration of specific antischistosomal antibodies. Serological assays are generally less sensitive, less specific and less reproducible than parasitological tests. Positive serological results do not indicate the intensity of infection or differentiate active or chronic infection. If their limitations are recognized and taken into account are serological tests of use in human schistosomiasis control. The diagnosis schistosomiasis should be based on a combination of clinical symptoms, history of residence in endemic or non-endemic areas, parasitological examinations, and serological findings.

Recently developed methods for the detection of babesial infections.

During the acute phase of babesiosis the direct identification of the causative agent is possible by examination of stained blood smears. An improved identification procedure for the diagnosis of Babesia bovis using DNA hybridization has been reported recently. For the diagnosis of both acute and chronic babesiosis, various serodiagnostic techniques have been developed. Recent advances in serodiagnosis designed for the detection of anti-Babesia antibodies were partly achieved by improving and standardizing the indirect immunofluorescence and complement fixation tests. The use of soluble antigens derived from Babesia culture supernatants or enriched, purified merozoites in the micro-enzyme-linked immunosorbent assay, solid phase radioimmunoassay and latex agglutination test has provided increased sensitivity and specificity in detecting anti-Babesia antibodies. Immunoblots and monoclonal antibodies have been used for the characterization and identification of babesial antigens and antigenic determinants. The advantages and disadvantages as well as the area of application of the currently available test systems will be discussed.

Functional reconstitution of skeletal muscle Ca2+ channels: separation of regulatory and channel components.

Regulatory properties of a partially purified Ca2+ -channel preparation from isolated rabbit skeletal muscle triads were examined in proteoliposomes. These properties included (i) inhibition by phenylalkylamine antagonists, such as verapamil, (ii) inhibition by the GTP-binding protein Go in the presence of guanosine 5'-[gamma-thio]triphosphate, and (iii) regulation of phenylalkylamine inhibition as a result of phosphorylation by a polypeptide-dependent protein kinase (PK-P). By selective reconstitution of protein fractions obtained by wheat germ lectin and ion-exchange chromatography, a separation of Ca2+-channel activity (fraction C) from regulatory component(s) (fraction R) responsible for verapamil sensitivity was achieved. Reconstitution of fraction C alone yielded vesicles that exhibited channel-mediated 45Ca2+ uptake that could be directly inhibited by coreconstitution of Go in the presence of guanosine 5'-[gamma-thio]triphosphate. However, the 45Ca2+ uptake obtained with fraction C was not inhibited by verapamil. Coreconstitution of fractions C and R yielded vesicles in which the sensitivity of 45Ca2+ uptake to verapamil was restored. The verapamil sensitivity of this preparation could be inhibited by PK-P. Fraction C, obtained by wheat germ agglutinin-Sepharose chromatography followed by DEAE-Sephacel chromatography, included a 180-kDa protein that was phosphorylated by cAMP-dependent protein kinase (PK-A) but not by PK-P and a 145-kDa protein (180 kDa under nonreducing conditions) that was not phosphorylated by either kinase. Fraction R contained proteins that did not adsorb to wheat germ lectin and included 165-kDa and 55-kDa proteins that were phosphorylated by PK-P but not by PK-A. These results suggest a complex model for Ca2+-channel regulation in skeletal muscle involving a number of distinct, separable protein components.

Ca2+ channel blockers interact with alpha 2-adrenergic receptors in rabbit ileum.

An interaction between Ca2+ channel blockers and alpha 2-adrenergic receptors has been demonstrated in rabbit ileum by studying the effect of clonidine on active electrolyte transport, under short-circuited conditions, in the presence and absence of several Ca2+ channel blocking agents. Clonidine, verapamil, diltiazem, cadmium, and nitrendipine all decrease short-circuit current and stimulate NaCl absorption to different extents with clonidine having the largest effect. Exposure to verapamil, diltiazem, and cadmium inhibited the effects of clonidine on transport, whereas nitrendipine had no such effect. Verapamil, diltiazem, and cadmium, but not nitrendipine, also decreased the specific binding of [3H]alpha 2-adrenergic agents to a preparation of ileal basolateral membranes explaining the observed decrease in the transport effects of clonidine. The effective concentrations of the Ca2+ channel blockers that inhibited the effects of clonidine on transport were fairly similar to the concentrations needed to inhibit its specific binding. The displacement of clonidine by calcium channel blockers is ascribed to a nonspecific effect of these agents, although the possibility that their effects are exerted via their binding to the calcium channels is not excluded.

Pharmacological characterization of two calcium currents in GH3 cells.

Whole cell patch-clamp techniques were used to investigate the pharmacological properties of calcium currents in the clonal rat pituitary cell line GH3. Current traces induced by a 100-ms pulse to 0 mV from a holding potential of -80 mV consisted of a component that rapidly inactivated during the pulse and a component that slowly inactivated during the pulse. When the holding potential was reduced to -32 mV, the rapidly inactivating component of the trace disappeared. The dihydropyridine calcium channel blocker nitrendipine affected only the slowly inactivating component of the trace. At a holding potential of -80 mV, nitrendipine blocked the slowly inactivating current with an IC50 of 1 microM. The IC50 for nitrendipine was found to be dependent on the holding potential, decreasing to 10 nM when the holding potential was -32 mV. The dihydropyridine agonist Bay-K 8644, like nitrendipine, affected only the slowly inactivating component. The inorganic blocker Cd2+ blocked both components but the slowly inactivating current was three- to fourfold more sensitive. These results are best explained by the existence of two types of calcium channels in these cells, one sensitive to dihydropyridines and one insensitive to dihydropyridines. These channels appear analogous to the T-type channel (inactivating current) and L-type channel (slowly inactivating current) described in other preparations.