Control of Calcium Channel Expression by Cellular ras Genes
{'Code': '08060200', 'Directorate': {'Abbreviation': 'BIO', 'LongName': 'Direct For Biological Sciences'}, 'Division': {'Abbreviation': 'DCB', 'LongName': 'Division of Cellular Biosciences'}}
{'SignBlockName': 'Vincent P. Gutschick', 'PO_EMAI': None, 'PO_PHON': None}
The mechanisms underlying the ontogeny of voltage-gated ion                channels in muscle are unknown.  To determine whether expression of             voltage-gated channels is dependent on mitogen withdrawal and growth            arrest, as is generally true for the induction of muscle specific gene          products, the BC3H1 muscle cell line is being used as an advantageous           model system.  Differentiated BC3H1 myocytes form functional calcium            and sodium channels which, by patch clamp techniques were found to              correspond to those in transverse tubules of skeletal muscle.  Ca and           Na channels were first detected about 4 days after mitogen withdrawal.          Since cellular ras genes have been found to have a role in the                  transduction of growth factor signals, BC3H1 cells have been modified           with an activated ras expression vector.  Transfection with a valine-12         c-Ha-ras vector suppressed the formation of functional Ca channels and          Na channels for more than 4 weeks.  In contrast, potassium channels             were affected neither by mitogenic medium nor by the transfected ras            gene.  Thus, the ras gene selectively blocked the expression of ion             channels whose induction was contingent upon mitogen withdrawal.  These         studies will be extended to elucidate the mechanisms that control Ca            channel number.  First, Ca channels expressed by differentiated BC3H1           muscle cells will be thoroughly characterized.  Second, growth factors          that inhibit muscle-specific gene expression in BC3H1 cells will be             used under conditions that uncouple direct effects from secondary               effects of cell proliferation.  Third, Ca channel expression will be            investigated in BC3H1 myocytes modified with genes that affect                  myogenesis.  These studies will focus on the control of Ca channel              expression by cellular ras genes and will analyze the effects produced          by a reversibly inducible ras expression vector, by a graded series of          missense mutations at codon 12 of the c-Ha-ras gene, by microinjected           ras proteins, and by blocking antibodies against p21 ras.                            This research represents one of the first major efforts to                 elucidate the genetic mechanisms regulating the expression of specific          voltage-dependent ion channels in muscle membranes.  The proposed               experiments should clarify the role of the cellular Ha-ras gene in the          control of calcium channel expression during muscle differentiation.
{'FirstName': 'Michael', 'LastName': 'Schneider', 'PI_MID_INIT': 'D', 'PI_SUFX_NAME': None, 'PI_FULL_NAME': 'Michael D Schneider', 'EmailAddress': 'michaels@bcm.tmc.edu', 'PI_PHON': '7137986913', 'NSF_ID': '000225332', 'StartDate': '09/01/1987', 'EndDate': None, 'RoleCode': 'Principal Investigator'}
{'Name': 'Baylor College of Medicine', 'CityName': 'HOUSTON', 'ZipCode': '770303411', 'PhoneNumber': '7137981297', 'StreetAddress': '1 BAYLOR PLZ', 'StreetAddress2': None, 'CountryName': 'United States', 'StateName': 'Texas', 'StateCode': 'TX', 'CONGRESSDISTRICT': '09', 'CONGRESS_DISTRICT_ORG': 'TX09', 'ORG_UEI_NUM': 'FXKMA43NTV21', 'ORG_LGL_BUS_NAME': 'BAYLOR COLLEGE OF MEDICINE', 'ORG_PRNT_UEI_NUM': 'FXKMA43NTV21'}
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[{'Code': '1117', 'Text': 'CELLULAR PHYSIOLOGY'}, {'Code': '1141', 'Text': 'PHYSIOLOG & STRUCTURAL SYS'}]
{'url': 'https://www.nsf.gov/awardsearch/download?DownloadFileName=1987&All=true', 'xml': '8711313.xml'}