Friday, April 19, 2024 4/19/2024

Fluctuations in Ionic Current through Membrane Channels

Award Number: R01NS021501
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

View Award Abstract

Of the dozen or so solved structures of voltage-gated ion channels (VGICs), only those of a weakly voltage-dependent Arabidopsis channel show the channel in its resting, de-activated state. Structures of VGIC voltage sensors in their resting “down” position are lacking because when solubilized in detergent or even reconstituted into nanodiscs, the absence of a membrane potential always leaves the voltage sensors in an activated or inactivated-relaxed conformation. In the proposed work innovative single-particle cryo-EM methods will be applied to obtain structures VGIC proteins as reconstituted into lipid vesicles. In the previous funding period we have made many methodological advances and have progressed to the point of obtaining nanometer/sub-nanometer cryo-EM structures of the Kv1.2 wildtype and “paddle chimera” potassium channel constructs, reconstituted into vesicles. In these structures no membrane potential is applied. We now propose to extend that work to higher resolution and to the resting-state structure of Kv1.2, the best-understood mammalian VGIC, by subjecting it to a large negative membrane potential. We will then acqure resting-state and activated-state structures of the Nav1.7 sodium channel, which is of intense interest as a central player and drug target in pain sensation. These structures will enable for the first time a quantitative understanding of VGIC voltage sensing, and mechanisms of pain disorders due to sodium channel mutations.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $436,353 )
2024	2024	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	NEW HAVEN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	37	1/18/2024	NON-COMPETING CONTINUATION	$436,353
														Subtotal = $436,353

Issue Date FY: 2023 ( Subtotal = $484,835 )
2023	2023	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	NEW HAVEN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	36	1/28/2023	NON-COMPETING CONTINUATION	$484,835
														Subtotal = $484,835

Issue Date FY: 2022 ( Subtotal = $536,859 )
2022	2022	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	NEW HAVEN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	35	1/11/2022	NON-COMPETING CONTINUATION	$483,174
2022	2022	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	NEW HAVEN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	35	3/28/2022	NON-COMPETING CONTINUATION	$53,685
														Subtotal = $536,859

Issue Date FY: 2021 ( Subtotal = $536,859 )
2021	2021	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	NEW HAVEN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	34	1/15/2021	NON-COMPETING CONTINUATION	$536,859
														Subtotal = $536,859

Issue Date FY: 2020 ( Subtotal = $553,679 )
2020	2020	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	NEW HAVEN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	33	2/12/2020	COMPETING CONTINUATION	$553,679
														Subtotal = $553,679

Issue Date FY: 2019 ( Subtotal = $0 )
2019	2017	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	NEW HAVEN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	32	11/21/2018	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2017 ( Subtotal = $396,493 )
2017	2017	YALE UNIVERSITY	105 WALL ST	NEW HAVEN	CT	06511	NEW HAVEN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	32	6/12/2017	NON-COMPETING CONTINUATION	$396,493
														Subtotal = $396,493

Issue Date FY: 2016 ( Subtotal = $396,493 )
2016	2016	YALE UNIVERSITY	47 College Street	NEW HAVEN	CT	06520	NEW HAVEN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	31	7/8/2016	NON-COMPETING CONTINUATION	$396,493
														Subtotal = $396,493

Issue Date FY: 2015 ( Subtotal = $396,493 )
2015	2015	YALE UNIVERSITY	47 College Street	NEW HAVEN	CT	06520	NEW HAVEN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	30	6/8/2015	NON-COMPETING CONTINUATION	$396,493
														Subtotal = $396,493

Issue Date FY: 2014 ( Subtotal = $402,268 )
2014	2014	YALE UNIVERSITY	47 College Street	NEW HAVEN	CT	06520	NEW HAVEN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	29	8/8/2014	COMPETING CONTINUATION	$402,268
														Subtotal = $402,268

Issue Date FY: 2012 ( Subtotal = $416,432 )
2012	2012	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	NEW HAVEN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	28	6/13/2012	NON-COMPETING CONTINUATION	$416,432
														Subtotal = $416,432

Issue Date FY: 2011 ( Subtotal = $407,971 )
2011	2011	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	NEW HAVEN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	27	6/16/2011	NON-COMPETING CONTINUATION	$407,971
														Subtotal = $407,971

Issue Date FY: 2010 ( Subtotal = $504,376 )
2010	2010	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	NEW HAVEN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	25	5/18/2010	SUPPLEMENT FOR EXPANSION	$80,458
2010	2010	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	NEW HAVEN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	26	6/17/2010	NON-COMPETING CONTINUATION	$423,918
														Subtotal = $504,376

Issue Date FY: 2009 ( Subtotal = $420,291 )
2009	2009	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	NEW HAVEN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	25	7/1/2009	COMPETING CONTINUATION	$420,291
														Subtotal = $420,291

Issue Date FY: 2008 ( Subtotal = $577,064 )
2008	2008	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	NEW HAVEN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	24	12/12/2007	NON-COMPETING CONTINUATION	$577,064
														Subtotal = $577,064

Issue Date FY: 2007 ( Subtotal = $583,473 )
2007	2007	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	NEW HAVEN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	23	1/18/2007	NON-COMPETING CONTINUATION	$583,473
														Subtotal = $583,473

Issue Date FY: 2006 ( Subtotal = $583,397 )
2006	2006	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	NEW HAVEN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	22	5/4/2006	NON-COMPETING CONTINUATION	$583,397
														Subtotal = $583,397

Issue Date FY: 2005 ( Subtotal = $584,678 )
2005	2005	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	NEW HAVEN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	21	12/13/2004	COMPETING CONTINUATION	$584,678
														Subtotal = $584,678

Issue Date FY: 2004 ( Subtotal = $545,971 )
2004	2004	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	NEW HAVEN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	20	11/10/2003	NON-COMPETING CONTINUATION	$545,971
														Subtotal = $545,971

Issue Date FY: 2003 ( Subtotal = $570,115 )
2003	2003	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	NEW HAVEN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	19		NON-COMPETING CONTINUATION	$530,115
2003	2003	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	NEW HAVEN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	001	19	6/6/2003	SUPPLEMENT FOR EXPANSION	$40,000
														Subtotal = $570,115

Issue Date FY: 2002 ( Subtotal = $514,713 )
2002	2002	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	NEW HAVEN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	18	11/2/2001	NON-COMPETING CONTINUATION	$514,713
														Subtotal = $514,713

Issue Date FY: 2001 ( Subtotal = $499,751 )
2001	2001	YALE UNIVERSITY	PO BOX 208250	NEW HAVEN	CT	06520	NEW HAVEN	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	17	12/15/2000	NON-COMPETING CONTINUATION	$499,751
														Subtotal = $499,751

Issue Date FY: 2000 ( Subtotal = $551,265 )
2000	2000	YALE UNIVERSITY	47 College Street	NEW HAVEN	CT	06520	NEW HAVEN	USA	Biological Basis Research in the Neurosciences	000	16	12/14/1999	COMPETING CONTINUATION	$551,265
														Subtotal = $551,265

Issue Date FY: 1999 ( Subtotal = $448,308 ) (Continued on the next page)
Grand Total All Awards = $11,731,633

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Fluctuations in Ionic Current through Membrane Channels

Award Number: R01NS021501

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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