Acute Activation of Maxi-K Channels (
            <i>hSlo</i>
            ) by Estradiol Binding to the β Subunit

Valverde, Miguel A.; Rojas, Patricio; Amigo, Julio D.; Cosmelli, Diego; Orio, Patricio; Bahamonde, María Isabel; Mann, Giovanni E.; Vergara, Cecilia; Latorre, Ramón

doi:10.1126/science.285.5435.1929

Cited by 473 publications

(386 citation statements)

References 37 publications

(10 reference statements)

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“…However, the prevention of the growth stimulation of estradiol by IBTX suggests that the BK channel activity plays a central role in this growth stimulation. This is also in accordance with the previously shown direct activation of BK channels by 17b-estradiol (Valverde et al, 1999). Taken together, activation of BK channel might be a major target of 17b-estradiol in prostate cancer in the absence of KCNMA1 amplification and overexpression.…”

Section: Kcnma1 Amplification In Prostate Cancersupporting

confidence: 92%

“…Despite the traditional use of estrogens for the treatment of prostate cancer, it is now known that estrogens can also induce neoplastic transformation in the prostate (Ho, 2004). In addition, 17b-estradiol directly activates BK channels by binding to the b1-regulatory subunit, as shown in vascular smooth muscle cells (Valverde et al, 1999). The present data provide evidence that 17b-estradiol stimulates growth of prostate cells through activation of BK channels.…”

Section: Kcnma1 Amplification In Prostate Cancersupporting

confidence: 54%

“…Other Ca 2 þ -activated K þ channels such as small and intermediate conductance channels showed negligible contribution to the whole-cell conductance of PC-3 and BPH-1 cells (data not shown). The whole-cell K þ conductance could not be augmented by the BK channel activator 17b-estradiol in PC-3 (Valverde et al, 1999), but was further enhanced along with a hyperpolarization of the membrane voltage in BPH-1 (Figure 4d). The results suggest a high activity of BK channels in PC-3 that cannot be further increased by 17b-estradiol.…”

Section: Bk Channel Currents In Prostate Cancer Cellsmentioning

confidence: 98%

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KCNMA1 gene amplification promotes tumor cell proliferation in human prostate cancer

et al. 2006

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Section: Kcnma1 Amplification In Prostate Cancersupporting

confidence: 92%

Section: Kcnma1 Amplification In Prostate Cancersupporting

confidence: 54%

Section: Bk Channel Currents In Prostate Cancer Cellsmentioning

confidence: 98%

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KCNMA1 gene amplification promotes tumor cell proliferation in human prostate cancer

et al. 2006

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“…It is possible that estrogen may produce vascular relaxation in an NO-independent manner by stimulating smooth muscle Maxi-K channel gates directly. 27 Leukocyte adhesion and infiltration occurs after SCI and intercellular adhesion molecules, such as ICAM-1 and P-selectin, play important roles in these processes. Estrogen may also improve blood flow after CNS injury by reducing leukocyte adhesion, which occludes small vessels.…”

Section: Discussionmentioning

confidence: 99%

Gender-related differences in recovery of locomotor function after spinal cord injury in mice

Farooque

Suo

et al. 2005

Spinal Cord

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Study design: In order to study the role of gender in recovery, we induced a thoracic compression spinal cord injury (SCI) separately in 2-month-old male and female C57Bl/6 mice. Objectives: We intended to assess effects of gender on recovery of hindlimb motor function and to correlate these with histomorphologic profiles of injured spinal cord tissue. Methods: Locomotor function was evaluated by three means: a modified locomotor scoring system for rodents, beam walking and computerized activity meter. Histology was analyzed by comparison of hematoxylin and eosin-stained perfused specimens. Results: Locomotor scores were 2.270.9 on day 1 in male mice, while, in contrast, they were significantly higher, 7.371.7, in females (Po0.02). On day 14 Basso, Beattie and Bresnahan scores were 9.572.2 in male mice and 16.072.2 in females (Po0.03). Terminal histology showed that the spinal cord architecture was relatively better preserved in female mice and that the extent of necrosis and infiltration of inflammatory cells was less compared to males. Setting: Neurobiology Research Laboratory of University of Kansas Medical School in US Department of Veterans Affairs Medical Center, Kansas City, Missouri. Conclusion: We found that the severity of the initial injury as well as the ultimate recovery of motor function after SCI is significantly influenced by gender, being remarkably better in females. The mechanism(s) of neuroprotection in females, although not yet elucidated, may be associated with the effects of estrogen on pathophysiological processes (blood flow, leukocyte migration inhibition, antioxidant properties, and inhibition of apoptosis).

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“…E 2 can also behave as an allosteric co-agonist of α 4 β 2 nicotinic receptors [190] or as an allosteric antagonist of NMDA receptors [277] and serotonin receptors 5-HT 3 [278]. Finally, the existence of a binding site for estrogens has also been identified on an ionic voltage-dependent channel, the high conductance calcium-dependent potassium-channel called maxi-K (hSlo, [263]). …”

Section: Non-genomic Effects On Cell Functionmentioning

confidence: 99%

Functional significance of the rapid regulation of brain estrogen action: Where do the estrogens come from?

2006

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Estrogens exert a wide variety of actions on reproductive and non-reproductive functions. These effects are mediated by slow and long lasting genomic as well as rapid and transient non-genomic mechanisms. Besides the host of studies demonstrating the role of genomic actions at the physiological and behavioral level, mounting evidence highlights the functional significance of non-genomic effects. However, the source of the rapid changes in estrogen availability that are necessary to sustain their fast actions is rarely questioned. For example, the rise of plasma estrogens at pro-estrus that represents one of the fastest documented changes in plasma estrogen concentration appears too slow to explain these actions. Alternatively, estrogen can be synthesized in the brain by the enzyme aromatase providing a source of locally high concentrations of the steroid. Furthermore, recent studies demonstrate that brain aromatase can be rapidly modulated by afferent inputs, including glutamatergic afferents. A role for rapid changes in estrogen production in the central nervous system is supported by experiments showing that acute aromatase inhibition affects nociception as well as male sexual behavior and that preoptic aromatase activity is rapidly (within min) modulated following mating. Such mechanisms thus fulfill the gap existing between the fast actions of estrogen and their mode of production and open new avenues for the understanding of estrogenic effects on the brain.

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Acute Activation of Maxi-K Channels ( hSlo ) by Estradiol Binding to the β Subunit

Cited by 473 publications

References 37 publications

KCNMA1 gene amplification promotes tumor cell proliferation in human prostate cancer

KCNMA1 gene amplification promotes tumor cell proliferation in human prostate cancer

Gender-related differences in recovery of locomotor function after spinal cord injury in mice

Functional significance of the rapid regulation of brain estrogen action: Where do the estrogens come from?

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