Biomedical subjects

M B Rook

Publications and source records attributed to M B Rook.

20 records · Page 2Linked to original sources

PubMed1988

Properties of single gap junctional channels between isolated neonatal rat heart cells.

The electrophysiological properties of single cardiac gap junctional channels that evolve one after another during the process of coupling between pairs of isolated neonatal rat heart myocytes obtained by enzymatic dispersion were investigated. Adjacent cells were brought in contact with each other by pushing them together by means of suction microelectrodes, which allow simultaneous voltage- or current-clamp recordings from each cell. Under these circumstances, the junctional channels had quite different properties from those reported in the literature. As long as only a few channels were present, they exhibited marked voltage-dependent gating as measured under voltage-clamp conditions and tended to close when transjunctional voltages greater than 50 mV were applied. Their single-channel conductance, depending on the composition of the solution in the recording pipettes, was approximately 45 or 60 pS, but also a lower conductance of 20 or 30 pS was encountered. As the junctional conductance increased concomitantly with an increase in the number of channels, this voltage dependence gradually diminished and eventually seemed to have disappeared completely. At that stage, the electrical properties of these newly formed junctions were identical with those of gap junctions between well-coupled cell pairs isolated as such.

Animals↗

PubMedDate not supplied

A single Na(+) channel mutation causing both long-QT and Brugada syndromes.

Mutations in SCN5A, the gene encoding the cardiac Na(+) channel, have been identified in 2 distinct diseases associated with sudden death: one form of the long-QT syndrome (LQT(3)) and the Brugada syndrome. We have screened SCN5A in a large 8-generation kindred characterized by a high incidence of nocturnal sudden death, and QT-interval prolongation and the "Brugada ECG" occurring in the same subjects. An insertion of 3 nucleotides (TGA) at position 5537, predicted to cause an insertion of aspartic acid (1795insD) in the C-terminal domain of the protein, was linked to the phenotype and was identified in all electrocardiographically affected family members. ECGs were obtained from 79 adults with a defined genetic status (carriers, n=43; noncarriers, n=36). In affected individuals, PR and QRS durations and QT intervals are prolonged (P<0.0001 for all parameters). ST segment elevation in the right precordial leads is present as well (P<0.0001). Twenty-five family members died suddenly, 16 of them during the night. Expression of wild-type and mutant Na(+) channels in Xenopus oocytes revealed that the 1795insD mutation gives rise to a 7.3-mV negative shift of the steady-state inactivation curve and an 8.1-mV positive shift of the steady-state activation curve. The functional consequence of both shifts is likely to be a reduced Na(+) current during the upstroke of the action potential. LQT(3) and Brugada syndrome are allelic disorders but may also share a common genotype.

Adult↗