title: Abnormal lithium and sodium transport in erythrocytes of a manic patient and some members of his family.
abstract: This paper compares the transport of Li(+) and Na(+) in erythrocytes from a patient with mania and from members of his family to that in erythrocytes from normal humans. In normal human erythrocytes, Li(+) is transported by at least three operationally distinct pathways: one inhibited by ouabain (ouabain-sensitive), one by phloretin (phloretin-sensitive), and one not inhibited by either compound (insensitive). Li(+) can be driven up its electrochemical potential gradient by an oppositely directed electrochemical potential gradient for Na(+)-i.e., Li(+)/Na(+) counterflow can occur-through the phloretin-sensitive pathway but not through the other two pathways. Because ouabain-sensitive Li(+) transport is negligible under physiological conditions, Li(+) distribution between erythrocytes and plasma in vivo depends mainly on the balance between Li(+)/Na(+) counterflow and the insensitive pathway(s) of Li(+) transport. The steady-state ratio of Li(+) concentration in the erythrocytes to that in the plasma of the patient was between 2 and 3 times higher than the comparable ratio in normal persons. The phloretin-sensitive Li(+)/Na(+) counterflow system was almost absent in the erythrocytes of the patient. Furthermore, unlike those from normal individuals, the patient's erythrocytes showed no external Li(+)-stimulated, phloretin-sensitive, ouabain-insensitive Na(+) efflux. The magnitudes of the ouabain-sensitive and insensitive pathways for Li(+) transport in the patient's erythrocytes were within normal limits. The decreased Li(+)/Na(+) counterflow in the patient's erythrocytes was probably not due to the presence of an inhibitor in the plasma of the patient but rather to an intrinsic defect in the erythrocytes. Because the father and several siblings of the patient showed a similar abnormality in erythrocyte Li(+)/Na(+) transport, it is probable that this defect is inherited.
mesh_terms: D000293:Adolescent; D000328:Adult; D001692:Biological Transport; D001693:Biological Transport, Active; D001714:Bipolar Disorder / Q000097:blood* / Q000188:drug therapy / Q000235:genetics; D002648:Child; D004910:Erythrocyte Membrane / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006801:Humans; D008094:Lithium / Q000097:blood* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010042:Ouabain / Q000494:pharmacology; D010693:Phloretin / Q000494:pharmacology; D012964:Sodium / Q000097:blood*
chemical_list: D010042:Ouabain; D008094:Lithium; D012964:Sodium; D010693:Phloretin
references.citation: J Gen Physiol. 1957 Nov 20;41(2):289-96
references.pmid: 13475692
references.citation: Lancet. 1976 Aug 21;2(7982):418-9
references.pmid: 73876
references.citation: Am J Psychiatry. 1974 Nov;131(11):1240-6
references.pmid: 4608979
references.citation: J Psychiatr Res. 1973 Jun;10(1):9-18
references.pmid: 4730006
references.citation: J Gen Physiol. 1976 Apr;67(4):433-67
references.pmid: 818340
references.citation: Am J Psychiatry. 1976 Aug;133(8):925-9
references.pmid: 782261
references.citation: Pflugers Arch. 1976 Jul 30;364(2):147-55
references.pmid: 986623
references.citation: Arch Gen Psychiatry. 1975 Sep;32(9):1097-102
references.pmid: 1237277
references.citation: Nature. 1975 Dec 4;258(5534):425-7
references.pmid: 1196375
references.citation: J Gen Physiol. 1971 Mar;57(3):259-82
references.pmid: 5544793
references.citation: Acta Physiol Scand. 1970 May;79(1):76-87
references.pmid: 5431014
references.citation: Nature. 1967 Sep 23;215(5108):1395-7
references.pmid: 6055461