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ROLES AND MECHANISMS OF SLO AND SLACK CHANNELS IN BRAIN

Award Number: P01NS042202
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/04/2001
PERIOD OF PERFORMANCE END DATE: 08/31/2006

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ROLES AND MECHANISMS OF SLO AND SLACK CHANNELS IN BRAIN - DESCRIPTION (provided by applicant): A class of calcium-activated potassium channels termed BK(Ca) channels are enriched at presynaptic neurotransmitter release sites within the brain, and are believed to control both the amount and timing of neurotransmitter release. BK(Ca) channels are encoded by the Slo gene. Recent evidence suggests that a related gene, Slack, also contributes to BK(Ca)-like channels in neurons, and that some BK(Ca) channels may be comprised of heteromultimers of Slo and Slack channels subunits. The experiments in this proposal will characterize the molecular, biophysical and structural properties of BK(Ca) channels in both the somata and presynaptic terminals of native neurons, and in transfected cells. The role of the Slo and Slack channel subunits in normal synaptic transmission, and the mechanisms of their response to hypoxia, will be determined by patch clamp measurements coupled with genetic knockout approaches. The structure and function of the large carboxy-terminal regulatory region of the Slo channel subunit with its calcium-binding sites, and its interaction with other proteins, including the Slack subunit, will be determined by biophysical and biochemical measurements and by X-ray crystallographic methods. Finally the structure of intact BK(Ca) channels will be determined by cryo-electronmicroscopy. Knowledge of the molecular properties and regulation of BK(Ca) channels in normal and hypoxic neurons, together with structural determinations of their interactions with both drugs and natural ligands, will be key in the development of more effective treatments for disorders such as epilepsy and stroke.


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: 2005 ( Subtotal = $1,557,397 )
2005	2005	YALE UNIVERSITY, SCHOOL OF MEDICINE	451 COLLEGE STREET, POB 1931	NEW HAVEN	CT	06409		USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	5	8/9/2005	NON-COMPETING CONTINUATION	$1,557,397
														Subtotal = $1,557,397

Issue Date FY: 2004 ( Subtotal = $1,511,008 )
2004	2004	YALE UNIVERSITY, SCHOOL OF MEDICINE	451 COLLEGE STREET, POB 1931	NEW HAVEN	CT	06409		USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	4	8/9/2004	NON-COMPETING CONTINUATION	$1,511,008
														Subtotal = $1,511,008

Issue Date FY: 2003 ( Subtotal = $1,466,089 )
2003	2003	YALE UNIVERSITY, SCHOOL OF MEDICINE	451 COLLEGE STREET, POB 1931	NEW HAVEN	CT	06409		USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	3	8/15/2003	NON-COMPETING CONTINUATION	$1,466,089
														Subtotal = $1,466,089

Issue Date FY: 2002 ( Subtotal = $1,438,661 )
2002	2002	YALE UNIVERSITY, SCHOOL OF MEDICINE	451 COLLEGE STREET, POB 1931	NEW HAVEN	CT	06409		USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	2	9/23/2002	NON-COMPETING CONTINUATION	$1,438,661
														Subtotal = $1,438,661

Issue Date FY: 2001 ( Subtotal = $1,474,141 )
2001	2001	YALE UNIVERSITY, SCHOOL OF MEDICINE	451 COLLEGE STREET, POB 1931	NEW HAVEN	CT	06409		USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/4/2001	NEW	$1,474,141
														Subtotal = $1,474,141

Grand Total All Awards = $7,447,296

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ROLES AND MECHANISMS OF SLO AND SLACK CHANNELS IN BRAIN

Award Number: P01NS042202

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/04/2001

PERIOD OF PERFORMANCE END DATE: 08/31/2006

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