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FUNCTIONAL BASIS OF BRADYCARDIA IN CONGENITAL HEART BLOC

Award Number: F32HL073658
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 12/19/2003
PERIOD OF PERFORMANCE END DATE: 02/25/2005

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FUNCTIONAL BASIS OF BRADYCARDIA IN CONGENITAL HEART BLOC - DESCRIPTION (provided by applicant): The long-term goal is to elucidate the mechanisms underlying autoimmune-associated sinus bradycardia. Significant sinus bradycardia was observed in infants from mothers with anti-Ro/La autoantibodies, and in pups from Ro/La immunized mice. Recent findings that alphalD L-type Ca channel activates at as low as -65mV, and the fact that alphalD knock out mice exhibited unexpected significant sinus bradycardia, suggest that alpha1D plays important role in pacemaking activity of SA node. I hypothesize that L-type Ca channel alphalD subunit could be the preferential target for anti-Ro/La antibodies, and may contribute to the development of autoimmune-associated sinus bradycardia. Information to be gained from this proposal will provide novel diagnostic and therapeutic insights into the autoimmune-associated sinus bradycardia. The specific aims are: 1. To test the effect of anti-Ro/La antibodies on L-type Ca channel alphalD expressed in Xenopus oocytes, because of the unavailable pharmacological agent to separate L-type alphalD from alphalC current in native cells. 2. To test the effect of anti-Ro/La antibodies on L-type Ca current activity of SA node cells obtained from alpha1D+/+ mice and alpha1 D-I- mice. Whole-cell L-type Ca current density before and after application of anti-Ro/La antibodies will be recorded and compared using patch-clamp technique on SA node cells obtained from alphalD+/+ and from alphalD-/- transgenic mice. 3. To identify the expression of Ca channel alphalD subunit in human fetal heart SA node cells. Single cell RT-PCR and indirect immunostaining will be used since alphalD is also expressed in neuronal and vascular tissue.


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 = $13,882 )
2005	2005	NARROWS INSTITUTE FOR BIOMEDICAL RESEARCH, INC	800 POLY PLACE BOX 20	BROOKLYN	NY	11209	KINGS	USA	Cardiovascular Diseases Research	000	2	11/23/2004	NON-COMPETING CONTINUATION	$13,882
														Subtotal = $13,882

Issue Date FY: 2004 ( Subtotal = $56,536 )
2004	2004	NARROWS INSTITUTE FOR BIOMEDICAL RESEARCH, INC	800 POLY PLACE BOX 20	BROOKLYN	NY	11209	KINGS	USA	Cardiovascular Diseases Research	000	1	12/19/2003	NEW	$56,536
														Subtotal = $56,536

Grand Total All Awards = $70,418

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FUNCTIONAL BASIS OF BRADYCARDIA IN CONGENITAL HEART BLOC

Award Number: F32HL073658

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 12/19/2003

PERIOD OF PERFORMANCE END DATE: 02/25/2005

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