Are Calcium Channels More Important Than Calcium Influx for Cell Proliferation?

We investigated the effect of intraluminal pressure or stretch on the development of tone in the descending thoracic aorta from rats with aortic coarctation-induced hypertension of 7–14 days duration. Increments of pressure >100 mmHg decreased the diameter of thoracic aortas from hypertensive but not from normotensive rats. The pressure-induced constriction was not demonstrable in vessels superfused with calcium-free buffer. Stretched rings of aorta from hypertensive rats exhibited a calcium-dependent constrictor tone accompanied by elevated calcium influx that varied in relation to the degree of stretch. Blockers of l-type calcium channels and inhibitors of protein kinase C reduced both basal tone and calcium influx in aortic rings of hypertensive rats. Hence, the thoracic aorta of hypertensive rats expresses a pressure- and stretch-activated constrictor mechanism that relies on increased calcium influx throughl-type calcium channels via a protein kinase C-regulated pathway. The expression of such a constrictor mechanism is suggestive of acquired myogenic behavior.

Download Full-text

Gating of Single N-type Calcium Channels Recorded from Bullfrog Sympathetic Neurons

The Journal of General Physiology ◽

10.1085/jgp.113.1.111 ◽

1999 ◽

Vol 113 (1) ◽

pp. 111-124 ◽

Cited By ~ 23

Author(s):

Hye Kyung Lee ◽

Keith S. Elmslie

Keyword(s):

Calcium Channels ◽

Calcium Influx ◽

Sympathetic Neurons ◽

Channel Gating ◽

Open Probability ◽

Maximum Value ◽

Open Time ◽

Time Component ◽

Patch Technique ◽

Single Exponential

For many neurons, N-type calcium channels provide the primary pathway for calcium influx during an action potential. We investigated the gating properties of single N-type calcium channels using the cell-attached patch technique. With 100 mM Ba2+ in the pipet, mean N-channel open probability (Po, measured over 100 ms) increased with depolarization, but the range at a single voltage was large (e.g., Po at +40 mV ranged from 0.1 to 0.8). The open dwell time histograms were generally well fit by a single exponential with mean open time (τo) increasing from 0.7 ms at +10 mV to 3.1 ms at +40 mV. Shut time histograms were well fit by two exponentials. The brief shut time component (τsh1 = 0.3 ms) did not vary with the test potential, while the longer shut time component (τsh2) decreased with voltage from 18.9 ms at +10 mV to 2.3 ms at +40 mV. Although N-channel Po during individual sweeps at +40 mV was often high (∼0.8), mean Po was reduced by null sweeps, low Po gating, inactivation, and slow activation. The variability in mean Po across patches resulted from differences in the frequency these different gating processes were expressed by the channels. Runs analysis showed that null sweeps tended to be clustered in most patches, but that inactivating and slowly activating sweeps were generally distributed randomly. Low Po gating (Po = 0.2, τo = 1 ms at +40 mV) could be sustained for ∼1 min in some patches. The clustering of null sweeps and sweeps with low Po gating is consistent with the idea that they result from different modes of N-channel gating. While Po of the main N-channel gating state is high, the net Po is reduced to a maximum value of close to 0.5 by other gating processes.

Download Full-text

Subplasmalemmal hydrogen peroxide triggers calcium influx in gonadotropes

Journal of Biological Chemistry ◽

10.1074/jbc.ra118.001830 ◽

2018 ◽

Vol 293 (41) ◽

pp. 16028-16042 ◽

Cited By ~ 4

Author(s):

An K. Dang ◽

Nathan L. Chaplin ◽

Dilyara A. Murtazina ◽

Ulrich Boehm ◽

Colin M. Clay ◽

...

Keyword(s):

Hydrogen Peroxide ◽

Calcium Channels ◽

Nadph Oxidase ◽

Calcium Channel ◽

Anterior Pituitary ◽

Calcium Influx ◽

Ros Generation ◽

Primary Mouse ◽

The Impact ◽

Stimulation Of

Gonadotropin-releasing hormone (GnRH) stimulation of its eponymous receptor on the surface of endocrine anterior pituitary gonadotrope cells (gonadotropes) initiates multiple signaling cascades that culminate in the secretion of luteinizing and follicle-stimulating hormones, which have critical roles in fertility and reproduction. Enhanced luteinizing hormone biosynthesis, a necessary event for ovulation, requires a signaling pathway characterized by calcium influx through L-type calcium channels and subsequent activation of the mitogen-activated protein kinase extracellular signal-regulated kinase (ERK). We previously reported that highly localized subplasmalemmal calcium microdomains produced by L-type calcium channels (calcium sparklets) play an essential part in GnRH-dependent ERK activation. Similar to calcium, reactive oxygen species (ROS) are ubiquitous intracellular signaling molecules whose subcellular localization determines their specificity. To investigate the potential influence of oxidant signaling in gonadotropes, here we examined the impact of ROS generation on L-type calcium channel function. Total internal reflection fluorescence (TIRF) microscopy revealed that GnRH induces spatially restricted sites of ROS generation in gonadotrope-derived αT3-1 cells. Furthermore, GnRH-dependent stimulation of L-type calcium channels required intracellular hydrogen peroxide signaling in these cells and in primary mouse gonadotropes. NADPH oxidase and mitochondrial ROS generation were each necessary for GnRH-mediated stimulation of L-type calcium channels. Congruently, GnRH increased oxidation within subplasmalemmal mitochondria, and L-type calcium channel activity correlated strongly with the presence of adjacent mitochondria. Collectively, our results provide compelling evidence that NADPH oxidase activity and mitochondria-derived hydrogen peroxide signaling play a fundamental role in GnRH-dependent stimulation of L-type calcium channels in anterior pituitary gonadotropes.

Download Full-text

Increased calcium influx through L-type calcium channels in hippocampal neurons with exogenous expression of presenilin-1 ΔE9 mutant

Bulletin of Experimental Biology and Medicine ◽

10.47056/0365-9615-2021-172-12-792-796 ◽

2021 ◽

Vol 172 (12) ◽

pp. 792-796

Author(s):

K. V. Skobeleva ◽

◽

М. A. Ryazantseva ◽

Е. V. Kaznacheyeva ◽

◽

...

Keyword(s):

Calcium Channels ◽

Hippocampal Neurons ◽

Calcium Influx ◽

Presenilin 1 ◽

Exogenous Expression

Download Full-text

Presynaptic calcium channels in rat cortical synaptosomes: fast- kinetics of phasic calcium influx, channel inactivation, and relationship to nitrendipine receptors

Journal of Neuroscience ◽

10.1523/jneurosci.06-05-01349.1986 ◽

1986 ◽

Vol 6 (5) ◽

pp. 1349-1357 ◽

Cited By ~ 91

Author(s):

JB Suszkiw ◽

ME O'Leary ◽

MM Murawsky ◽

T Wang

Keyword(s):

Calcium Channels ◽

Calcium Influx ◽

Fast Kinetics ◽

Channel Inactivation ◽

Presynaptic Calcium ◽

Kinetics Of

Download Full-text

L-Type Calcium Channels Are Required for One Form of Hippocampal Mossy Fiber LTP

Journal of Neurophysiology ◽

10.1152/jn.1998.79.4.2181 ◽

1998 ◽

Vol 79 (4) ◽

pp. 2181-2190 ◽

Cited By ~ 102

Author(s):

Ajay Kapur ◽

Mark F. Yeckel ◽

Richard Gray ◽

Daniel Johnston

Keyword(s):

Calcium Channels ◽

High Frequency ◽

Pyramidal Neurons ◽

Mossy Fiber ◽

Calcium Influx ◽

Calcium Transients ◽

High Frequency Stimulation ◽

Frequency Stimulation ◽

Ca3 Pyramidal Neurons ◽

Postsynaptic Calcium

Kapur, Ajay, Mark F. Yeckel, Richard Gray, and Daniel Johnston. L-type calcium channels are required for one form of hippocampal mossy fiber LTP. J. Neurophysiol. 79: 2181–2190, 1998. The requirement of postsynaptic calcium influx via L-type channels for the induction of long-term potentiation (LTP) of mossy fiber input to CA3 pyramidal neurons was tested for two different patterns of stimulation. Two types of LTP-inducing stimuli were used based on the suggestion that one of them, brief high-frequency stimulation (B-HFS), induces LTP postsynaptically, whereas the other pattern, long high-frequency stimulation (L-HFS), induces mossy fiber LTP presynaptically. To test whether or not calcium influx into CA3 pyramidal neurons is necessary for LTP induced by either pattern of stimulation, nimodipine, a L-type calcium channel antagonist, was added during stimulation. In these experiments nimodipine blocked the induction of mossy fiber LTP when B-HFS was given [34 ± 5% (mean ± SE) increase in control versus 7 ± 4% in nimodipine, P < 0.003]; in contrast, nimodipine did not block the induction of LTP with L-HFS (107 ± 10% in control vs. 80 ± 9% in nimodipine, P > 0.05). Administration of nimodipine after the induction of LTP had no effect on the expression of LTP. In addition, B- and L-HFS delivered directly to commissural/associational fibers in stratum radiatum failed to induce a N-methyl-d-aspartate-independent form of LTP, obviating the possibility that the presumed mossy fiber LTP resulted from potentiation of other synapses. Nimodipine had no effect on calcium transients recorded from mossy fiber presynaptic terminals evoked with the B-HFS paradigm but reduced postsynaptic calcium transients. Our results support the hypothesis that induction of mossy fiber LTP by B-HFS is mediated postsynaptically and requires entry of calcium through L-type channels into CA3 neurons.

Download Full-text