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J Hescheler

Publications and source records attributed to J Hescheler.

At least 109 records · Page 6Linked to original sources
PubMed1994

Electrical activity and calcium channels in neuroendocrine cells.

Similar to neuronal cells, neuroendocrine cells express voltage-dependent ion channels and fire action potentials. Ca2+ influx through voltage-dependent Ca2+ channels couples changes in membrane potential to Ca(2+)-dependent cellular processes, such as hormone release. Using the patch-clamp technique, we studied the spontaneous electrical activity as well as voltage-dependent Ca2+ channels in cholecystokinin-producing pancreatic cells (RIN 1056E cell line), in prolactin-secreting pituitary cells (GH3 cell line), and in calcitonin-secreting cells of the thyroid (rMTC 44-2 cell line). All three cell types displayed spontaneous electrical activity, that is, they spontaneously produced action potentials. RIN 1056E cells, GH3 cells, and rMTC cells exhibited (various types of) voltage-dependent Ca2+ channels that were regulated by various neurotransmitters and hormones, such as somatostatin.

Action Potentials↗
PubMed1994

Double-pulse facilitation of smooth muscle alpha 1-subunit Ca2+ channels expressed in CHO cells.

Frequent strong depolarizations facilitate Ca2+ channels in various cell types by shifting their gating behavior towards mode 2, which is characterized by long openings and high probability of being open. In cardiac cells, the same type of gating behavior is potentiated by beta-adrenoceptors presumably acting via phosphorylation of a protein identical to or associated with the channel. Voltage-dependent phosphorylation has also been reported to underlie Ca2+ channel facilitation in chromaffin adrenal medulla and in skeletal muscle cells. We studied a possible voltage-dependent facilitation of the principal channel forming alpha 1-subunit of the dihydropyridine-sensitive smooth muscle Ca2+ channel. Single channel and whole-cell Ca2+ currents were recorded in Chinese hamster ovary cells stably expressing the class Cb Ca2+ channel alpha 1-subunit. Strong depolarizing voltage-clamp steps preceding the test pulse resulted in a 2- to 3-fold increase of the single Ca2+ channel activity and induction of mode 2-like gating behavior. Accordingly we observed a significant potentiation of the whole-cell current by approximately 50%. In contrast to the previous suggestions we found no experimental evidence for involvement of channel phosphorylation by protein kinases (cAMP-dependent protein kinase, protein kinase C and other protein kinases utilizing ATP gamma S) in the control and facilitated current. The data demonstrate that the L-type Ca2+ channel alpha 1-subunit solely expressed in Chinese hamster ovary cells is subject to a voltage-dependent facilitation but not to phosphorylation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Muscle cell differentiation of embryonic stem cells reflects myogenesis in vivo: developmentally regulated expression of myogenic determination genes and functional expression of ionic currents.

The mouse blastocyst-derived embryonic stem cell (ES cell) line BLC6 efficiently differentiates into myosin heavy chain-, desmin- and myogenin-positive skeletal muscle cells when cultivated in embryo-like aggregates (embryoid bodies). Here, we show that the muscle-specific determination genes myf5, myogenin, myoD, and myf6 are expressed in these embryoid bodies in a characteristic temporal pattern which precisely reflects the sequence observed during mouse development in vivo. Myf5 is the first gene to be expressed followed by myogenin, myoD, and myf6, in this order. In situ hybridization demonstrates transcripts for myogenin and myoD accumulating in mono- and multinucleated myogenic cells, while myf5 mRNA is already found in mononucleated myoblasts. The myocytes also express functional nicotinic cholinoceptors and exhibit T-type Ca2+ currents and later L-type Ca2+ currents, demonstrating physiological properties of skeletal muscle cells. During myocyte differentiation the density of L-type Ca2+ channels significantly increases while the density of T-type Ca2+ channels decreases. The effect of external signals on myogenic differentiation of BLC6 cells was demonstrated by cocultivation with visceral endodermal END-2 cells and the activin A-secreting WEHI-3 cells. END-2 cells essentially prevent skeletal muscle differentiation, whereas basic fibroblast growth factor, transforming growth factor-beta, and WEHI-3 cells have no or an attenuating effect, respectively. Our results suggest that ES cells recapitulate closely the early steps of muscle development in vivo and may serve as an excellent in vitro system to study this process.

Animals↗
PubMed1994

The isoquinoline derivative LOE 908 selectively blocks vasopressin-activated nonselective cation currents in A7r5 aortic smooth muscle cells.

The effect of (R,S)-(3,4-dihydro 6,7-dimethoxy-isoquinoline-1-yl)-2-phenyl- N,N-di-[2-(2,3,4-trimethoxyphenyl)ethyl]-acetamide (LOE 908), a cation channel blocker in HL-60 promyeloblasts, was studied in the A7r5 smooth muscle cell line from rat thoracic aorta, using the whole-cell patch-clamp technique. At a holding potential of -60 mV, application of vasopressin induced a nonselective cation conductance in voltage-clamped A7r5 cells. The current-voltage relation was linear, and currents reversed close to 0 mV regardless of the chloride gradient. The activation of the nonselective cation conductance by vasopressin was not affected by dialysing cells with Ca(2+)-free internal solution. LOE 908 blocked this current in a concentration-dependent manner with an IC50 of 560 nM, whereas dihydropyridine-sensitive Ba2+ current through voltage-dependent Ca2+ channels was blocked with an IC50 of 28 microM. Another organic blocker of receptor-mediated Ca2+ entry, 1-beta-[3-(4-methoxyphenyl)-propoxy]-4-methoxyphenethyl-1H-imidazole hydrochloride (SK&F 96365), blocked both, the vasopressin-induced nonselective conductance and the voltage-activated Ba2+ current with similar IC50 values of 13 microM and 8 microM, respectively. The rank order of potency of inorganic blockers on the vasopressin-induced inward current was Gd3+ > La3+ > Cd2+. Vasopressin-induced non-selective cation current was also observed in pertussis toxin-pretreated A7r5 cells but was completely abolished after infusion of the GDP analogue, guanosine 5'-O-[3-thio]diphosphate, from the patch pipette. Furthermore, vasopressin induced a transient outward current, suggesting a Ca(2+)-activated K(+)-current, which overlapped with the nonselective cation conductance.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetamides↗
PubMed1994

Cardiomyocyte-like cells differentiated in vitro from embryonic carcinoma cells P19 are characterized by functional expression of adrenoceptors and Ca2+ channels.

P19 embryonal carcinoma cells were differentiated via embryolike aggregates (embryoid bodies) into spontaneously beating myocytes. During the whole process of differentiation the functional expression of cardiac-specific receptors and ionic channels was characterized by measuring the chronotropic reactivity, action potentials, and ionic currents in response to various cardioactive drugs. Positive chronotropic effects obtained at different maximal effective concentrations of adrenoceptor-mediated agonists indicated differential adrenoceptor expression during the in vitro development of cardiomyocyte-like cells. No cardiac-specific response was obtained with the muscarinic cholinoceptor agonist carbachol. Single beating cells were enzymatically isolated and investigated by the patch-clamp technique. Pacemaker action potentials similar to those of embryonal cardiomyocytes exhibited amplitudes ranging from 50 to 85 mV. The action potentials were synchronous to the mechanical contractions and, comparable to the chronotropic effects, were modulated by BayK 8644, isradipine, and adrenaline. The functional expression of L-type Ca2+ channels was demonstrated by the Ca2+ channel blockers isradipine, nisoldipine, gallopamil, and diltiazem causing negative chronotropic responses, as well as by the Ca2+ channel activator BayK 8644 causing positive chronotropic responses. These effects gradually increased with time of differentiation. The expression of L-type Ca2+ channels and of nicotinic acetylcholine receptors was confirmed in voltage-clamp experiments. The study demonstrates that P19 embryonal carcinoma cells can be induced to differentiate into cardiomyocyte-like cells comparable to embryonal and neonatal heart cells lacking the muscarinic cholinoceptor response only.

Action Potentials↗
PubMed1994

Cardiomyocytes differentiated in vitro from embryonic stem cells developmentally express cardiac-specific genes and ionic currents.

Cardiomyocytes differentiated in vitro from pluripotent embryonic stem (ES) cells of line D3 via embryo-like aggregates (embryoid bodies) were characterized by the whole-cell patch-clamp technique during the entire differentiation period. Spontaneously contracting cardiomyocytes were enzymatically isolated by collagenase from embryoid body outgrowths of early, intermediate, and terminal differentiation stages. The early differentiated cardiomyocytes exhibited an outwardly rectifying, transient K+ current sensitive to 4-aminopyridine and an inward Ca2+ current but no Na+ current. The Ca2+ current showed all features of L-type Ca2+ current, being highly sensitive to 1,4-dihydropyridines but not to omega-conotoxin. Cardiomyocytes of intermediate stage were characterized by the additional expression of cardiac-specific Na+ current, the delayed K+ current, and If current. Terminally differentiated cardiomyocytes expressed a Ca2+ channel density about three times higher than that of early stage. In addition, two types of inwardly rectifying K+ currents (IK1 and IK,Ach) and the ATP-modulated K+ current were found. During cardiomyocyte differentiation, several distinct cell populations could be distinguished by their sets of ionic channels and typical action potentials presumably representing cardiac tissues with properties of sinus node, atrium, and ventricle. Reverse transcription polymerase chain reaction revealed the transcription of alpha- and beta-cardiac myosin heavy chain (MHC) genes synchronously with the first spontaneous contractions. Transcription of embryonic skeletal MHC gene at intermediate and terminal differentiation stages correlated with the expression of Na+ channels. The selective expression of alpha-cardiac MHC gene in ES cell-derived cardiomyocytes was demonstrated after ES cell transfection of the LacZ construct driven by the alpha-cardiac MHC promoter region followed by ES cell differentiation and beta-galactosidase staining. In conclusion, our data demonstrate that ES cell-derived cardiomyocytes represent a unique model to investigate the early cardiac development and permit pharmacological/toxicological studies in vitro.

Animals↗
PubMed1993

Inversion of Ca2+ current modulation during recovery of neuroblastoma cells from pertussis toxin pretreatment.

Human neuroblastoma cells (SH-SY5Y) differentiated by retinoic acid exhibited high threshold-activated N-type Ca2+ currents, which were largely inhibited by the two enkephalins, DAGO and DPDPE, as well as by dopamine and somatostatin. The inhibitory effects were fully abolished after pretreatment of cells with pertussis toxin. After washing out the toxin, the inhibitory effects re-established with a time constant of about 16 h. The recovery of Ca2+ current inhibition was similar for all tested agonists. Unexpectedly, we observed a neurotransmitter-induced stimulation of Ca2+ currents in approximately 10% of all investigated cells during the recovery phase. Such a stimulatory effect by otherwise inhibitory receptors was never seen in control cells. It did also not occur when exogenous purified G-proteins of the Gi family were reconstituted via the patch pipette, suggesting that additional mechanisms may play a role in the appearance of stimulatory effects during the recovery phase after pertussis toxin pretreatment.

Calcium↗
PubMed1993

Gi2 and protein kinase C are required for thyrotropin-releasing hormone-induced stimulation of voltage-dependent Ca2+ channels in rat pituitary GH3 cells.

In rat pituitary GH3 cells, thyrotropin-releasing hormone (TRH) and other secretion-stimulating hormones trigger an increase in the cytosolic Ca2+ concentration by two mechanisms. Ca2+ is released from intracellular stores in response to inositol 1,4,5-trisphosphate and can enter the cell through voltage-dependent L-type Ca2+ channels. Stimulation of these channels is sensitive to pertussis toxin, indicating that a pertussis toxin-sensitive heterotrimeric guanine nucleotide-binding regulatory protein (G protein) is involved in functional coupling of the receptor to the Ca2+ channel. We identified the G protein involved in the stimulatory effect of TRH on the Ca2+ channel by type-selective suppression of G-protein synthesis. Antisense oligonucleotides were microinjected into GH3 cell nuclei, and 48 h after injection the TRH effect was tested. Whereas antisense oligonucleotides hybridizing to the mRNA of G(o) or Gi1 alpha-subunit sequences did not affect stimulation by TRH, oligonucleotides suppressing the expression of the Gi2 alpha subunit abolished this effect, and oligonucleotides directed against the mRNA of the Gi3 alpha subunit had less effect. The requirement of a concurrent inositol phospholipid degradation and subsequent protein kinase C (PKC) activation for the TRH effect on Ca(2+)-channel activity was demonstrated by inhibitory effects of antisense oligonucleotides directed against Gq/G11/Gz alpha-subunit sequences and treatment of GH3 cells with PKC inhibitors, respectively. Our results suggest that TRH elevates the cytosolic Ca2+ concentration in GH3 cells transiently via Ca2+ release from internal stores, followed by a phase of sustained Ca2+ influx through voltage-dependent Ca2+ channels stimulated by the concerted action of Gi2 (and Gi3) plus PKC.

Animals↗
PubMed1993

Selectivity in signal transduction determined by gamma subunits of heterotrimeric G proteins.

Various heterotrimeric guanine nucleotide-binding proteins have been identified on the basis of the individual subtypes of their alpha subunits. The beta gamma complexes, composed of beta and gamma subunits, remain tightly associated under physiological conditions and have been assumed to constitute a common pool shared among various guanosine triphosphate (GTP)-binding (G) protein heterotrimers. Particular alpha and beta subunit subtypes participate in the signal transduction processes between somatostatin or muscarinic receptors and the voltage-sensitive L-type calcium channel in rat pituitary GH3 cells. Among gamma subunits the gamma 3 subtype was found to be required for coupling of the somatostatin receptor to voltage-sensitive calcium channels, whereas the gamma 4 subtype was found to be required for coupling of the muscarinic receptor to those channels.

Animals↗
PubMed1993

Dihydropyridine binding and Ca(2+)-channel characterization in clonal calcitonin-secreting cells.

1,4-Dihydropyridine-sensitive voltage-dependent Ca2+ channels play a crucial role in the extracellular Ca(2+)-sensing of calcitonin-secreting parafollicular cells of the thyroid (C-cells). To characterize the Ca2+ channels in C-cells, we studied 1,4-dihydropyridine binding and performed electrophysiological experiments with Ca(2+)-sensitive C-cells (rat C-cell line rMTC 44-2) in comparison with 'defective' Ca(2+)-insensitive C-cells (human C-cell line TT). In membranes of rMTC cells, we detected a high-affinity, stereoselective and Ca(2+)-dependent binding site for the Ca(2+)-channel-blocking 1,4-dihydropyridine, (+)-[3H]PN 200-110. Radioligand binding was saturable (Bmax. = 18 +/- 2 fmol/mg of protein), reversible [Ki for (+)-PN 200-110 = 37 +/- 1 pM) and allosterically modulated by the phenylalkylamine (-)-desmethoxyverapamil [(-)-D888] as well as the bis-benzylisoquinoline alkaloid (+)-tetrandrine. Thus the 1,4-dihydropyridine binding in rMTC cells featured all characteristics of binding to the alpha 1-subunit of L-type Ca2+ channels. In contrast, in membranes of TT cells, which are known to lack Ca(2+)-sensitivity, no Ca(2+)-channel-specific (+)-[3H]PN 200-110 binding was detected. In voltage-clamp experiments, rMTC cells exhibited slowly inactivating Ca2+ currents which proved sensitive to (+)-PN 200-110, (-)-D888 and (+)-tetrandrine. These L-type Ca(2+)-channel blockers did not affect the Ca2+ currents in TT cells. The numbers of 1,4-dihydropyridine-sensitive Ca2+ channels in rMTC cells as calculated from both the binding studies and the whole-cell/single-channel recordings were 2000 and 7000/cell respectively. Thus qualitative and quantitative detection of 1,4-dihydropyridine-sensitive Ca2+ channels by radioligand-binding in Ca(2+)-sensitive rMTC cells, but not in Ca(2+)-insensitive TT cells, reflects the electrophysiological detection of functional Ca2+ channel in rMTC cells, but not in TT cells.

Alkaloids↗
PubMed1993

Nonselective cation channels: physiological and pharmacological modulations of channel activity.

Cation channels play a major role in fast and sustained cellular responses to hormones and neurotransmitters. They contribute to depolarization of the membrane and--in most cases--to an increase in the intracellular Ca2+ concentration. Nonselective cation channels presumably form a large family of diverse channels which are modulated by various extracellular and intracellular signals. Structure and regulation of ligand-operated and cyclic nucleotide-activated nonselective cation channels found in synapses and sensory receptor cells, respectively, are well documented; none of the structures of other cation channels are known. Except for ligand-operated and stretch-activated channels, G-proteins form the link between the involved receptors and signalling cascades stimulating nonselective cation channels. Observed in numerous cellular systems is hormonal activation of cation channels by hormones or neurotransmitters interacting with heptahelical receptors inducing a phosphoinositide breakdown (PI response); several pathways stimulated within the PI response may generate signals involved in cation channel activation. Pharmacological modifications of nonselective cation channels by inorganic and organic blockers are so far extremely limited; various blockers have been described but unfortunately lack high specificity for these channels.

Animals↗
PubMed1993

Cation channels in oocytes and early states of development: a novel type of nonselective cation channel activated by adrenaline in a clonal mesoderm-like cell line (MES-1).

The expression of receptors and ion channels alters during growth, maturation, and after fertilization of oocytes reflecting functional changes. Besides voltage-dependent ion channels, oocyte membranes possess an IP3-activated cation channel mediating a prolonged Ca2+ influx. The Ca2+ is thought to be involved in maturation and fertilization. Alternatively, mono- and divalent cations can enter oocytes via stretch-activated channels. The oocyte channel population is further modified during subsequent embryogenesis, suggesting that ionic channels obviously become expressed at specific states of embryological differentiation and in tissue-specific manner. The resulting differences in functional ion channel populations of adult cells underlie the large diversity of cells and their function. Conversely, differentiation and cell proliferation themselves depend on ion transport. Ca2+ ions have been shown to play a pivotal role in these processes. Nonselective cation channels represent one possible pathway for Ca2+ entry into the cell and, therefore, might be involved in the regulation of embryological development. Undifferentiated embryonal carcinoma cells (P19), visceral endoderm-like cells (END-2), epithelioid ectoderm-like cells (EPI-7), mesoderm-like cells (MES-1), and parietal yolk sac cells (PYS-2) have been used as a model to study the expression of ionic channels during early development. In MES-1 cells a nonselective cation current was activated by adrenaline. Interestingly, the intracellular pathway for activation of these channels involved the cascade of activation of the cAMP-dependent protein kinase (PKA) resulting in protein phosphorylation. This mechanism is well known for Ca2+ channel stimulation in cardiac and skeletal muscle both originating from the mesoderm.

Adenosine Triphosphate↗
PubMed1993

Voltage-dependent L-type Ca channels and a novel type of non-selective cation channel activated by cAMP-dependent phosphorylation in mesoderm-like (MES-1) cells.

Undifferentiated P19 embryonal carcinoma cells (ECC P19), the P19-derived clonal cell lines END-2 (visceral endoderm-like), EPI-7 (epithelioid ectoderm-like), MES-1 (mesoderm-like) and a parietal yolk sac cell line (PYS-2) were used as cellular models to examine the functional expression of voltage-dependent Ca channels and other Ca-permeable cation channels at various stages of early embryonic development. Whole-cell currents were recorded by means of the patch clamp technique. Whereas more than 75% of MES-1 cells possessed Ca channel currents, neither P19, END-2, EPI-7 nor PYS-2 cells had detectable voltage-dependent inward currents. Ca channel currents of MES-1 cells were highly sensitive towards 1,4-dihydropyridines and blocked by cadmium. Adrenaline (10 microM) caused Ca channel stimulation in only 14% of MES-1 cells examined. However, in 62% of the cells adrenaline activated a linear current component which under physiological conditions reversed close to 0 mV. Removal of extracellular Na+ suppressed the adrenaline-induced inward current, while reducing extracellular Cl- had no significant effect. These findings suggest that the adrenaline-induced current is carried through non-selective cation channels which were found to be permeable for Na+, K+, Cs+ >> Ca2+. Remarkably, the intracellular signalling pathway for activation of the non-selective cation current involved the cascade of reactions leading to cAMP-dependent phosphorylation, a regulatory pathway well known for cardiac Ca channels. A possible functional role of adrenaline-induced non-selective cation currents and Ca channels in embryonal development is discussed.

Calcium Channels↗
PubMed1993

Embryonic stem cells differentiate in vitro into cardiomyocytes representing sinusnodal, atrial and ventricular cell types.

Pluripotent embryonic stem cells (ESC, ES cells) of line D3 were differentiated in vitro and via embryo-like aggregates (embryoid bodies) of defined cell number into spontaneously beating cardiomyocytes. By using RT-PCR technique, alpha- and beta-cardiac myosin heavy chain (MHC) genes were found to be expressed in embryoid bodies of early to terminal differentiation stages. The exclusive expression of the beta-cardiac MHC gene detected in very early differentiated embryoid bodies proved to be dependent on the number of ES cells developing in the embryoid body. Cardiomyocytes enzymatically isolated from embryoid body outgrowths at different stages of development were further characterized by immunocytological and electrophysiological techniques. All cardiomyocytes appeared to be positive in immunofluorescence assays with monoclonal antibodies against cardiac-specific alpha-cardiac MHC, as well as muscle-specific sarcomeric myosin heavy chain and desmin. The patch-clamp technique allowed a more detailed characterization of the in vitro differentiated cardiomyocytes which were found to represent phenotypes corresponding to sinusnode, atrium or ventricle of the heart. The cardiac cells of early differentiated stage expressed pacemaker-like action potentials similar to those described for embryonic cardiomyocytes. The action potentials of terminally differentiated cells revealed shapes, pharmacological characteristics and hormonal regulation inherent to adult sinusnodal, atrial or ventricular cells. In cardiomyocytes of intermediate differentiation state, action potentials of very long duration (0.3-1 s) were found, which may represent developmentally controlled transitions between different types of action potentials. Therefore, the presented ES cell differentiation system permits the investigation of commitment and differentiation of embryonic cells into the cardiomyogenic lineage in vitro.

Action Potentials↗
PubMed1993

G-proteins involved in the calcium channel signalling system.

Various mechanisms have been identified by which hormones and neurotransmitters interacting with seven transmembrane alpha-helical spanning segments receptors modulate the activity of ion channels. All of the mechanisms involve heterotrimeric G-proteins; the best documented are hormonal modulations of voltage-dependent Ca2+ channels in cardiac, neuronal and endocrine cells. Recent studies using antisense oligonucleotide probes allow the exact identification of the G-proteins involved in these signal transduction pathways.

Animals↗
PubMed1993

cGMP-dependent protein kinase activates Ca-activated K channels in cerebral artery smooth muscle cells.

Guanosine-3',5'-cyclic monophosphate (cGMP)-dependent protein kinase (cGMP-PK) plays a central role in the mediation of the vasodilator response to nitric oxide (NO) and other nitrovasodilators. It is unclear whether cGMP-PK affects calcium-activated potassium channels (KCa channels) or any other type of ion channel in smooth muscle. We provide here the first direct evidence that cGMP-PK can activate KCa channels in arterial smooth muscle cells. We demonstrate that NO and a membrane-permeable analogue of cGMP can activate KCa channels in on-cell patches approximately twofold. Furthermore, cGMP-PK, in the presence of ATP and cGMP added directly to the intracellular surface of inside-out patches, increases channel activity by approximately eightfold. These results suggest that cGMP-PK-mediated activation of KCa channels may contribute to the actions of NO and other nitrovasodilators.

Animals↗
PubMed1993

Major role of dihydropyridine-sensitive Ca2+ channels in Ca(2+)-induced calcitonin secretion.

Endocrine cells are known to possess multiple types of Ca2+ channels. In neurons, omega-conotoxin-sensitive N-type Ca2+ channels have been shown to play a dominant role in neurotransmitter release, but uncertainty remains about the types of Ca2+ channels involved in stimulus-secretion coupling in endocrine cells. We investigated the relative contribution of 1,4-dihydropyridine-sensitive and omega-conotoxin-sensitive Ca2+ channels to Ca(2+)-induced calcitonin release in parafollicular cells of the thyroid (C cells). In whole cell voltage-clamp experiments, both 1,4-dihydropyridine-sensitive and omega-conotoxin-sensitive Ca2+ channel currents were identified. The dihydropyridine isradipine (1 microM) but not omega-conotoxin (1 microM) inhibited the steady-state Ca2+ influx at physiological membrane potentials, the spontaneous electrical activity, and calcitonin secretion (at 2-h incubations). Moreover, suppression of the spontaneous electrical activity by the Na+ channel blocker tetrodotoxin did not affect calcitonin release. We conclude that 1,4-dihydropyridine-sensitive Ca2+ channels play a major role in Ca(2+)-dependent calcitonin release and that calcitonin secretion due to Ca2+ influx proceeds even in the absence of action potentials.

Animals↗