Function of a truncated dihydropyridine receptor as both voltage sensor and calcium channel.

The skeletal muscle dihydropyridine (DHP) receptor serves dual functions, as a voltage sensor for excitation-contraction coupling and as an L-type calcium channel. Biochemical analysis indicates the presence of two forms of the DHP receptor polypeptide in skeletal muscle, a full-length translation product present as a minor species and a much more abundant form that has a truncated carboxy-terminus. On the basis of these and other observations, it has been proposed that, in skeletal muscle, only the full-length DHP receptor can function as a calcium channel and that the truncated form can only function as a voltage sensor for excitation-contraction coupling. To resolve this issue, we have now constructed a complementary DNA (pC6 delta 1) encoding a protein corresponding to the truncated DHP receptor in skeletal muscle. Expression of pC6 delta 1 in dysgenic myotubes fully restores both excitation-contraction coupling and calcium current, consistent with the idea that a single class of DHP receptors performs both functions.     

Widespread horizontal transfer of mitochondrial genes in flowering plants

Horizontal gene transfer--the exchange of genes across mating barriers--is recognized as a major force in bacterial evolution. However, in eukaryotes it is prevalent only in certain phagotrophic protists and limited largely to the ancient acquisition of bacterial genes. Although the human genome was initially reported to contain over 100 genes acquired during vertebrate evolution from bacteria, this claim was immediately and repeatedly rebutted. Moreover, horizontal transfer is unknown within the evolution of animals, plants and fungi except in the special context of mobile genetic elements. Here we show, however, that standard mitochondrial genes, encoding ribosomal and respiratory proteins, are subject to evolutionarily frequent horizontal transfer between distantly related flowering plants. These transfers have created a variety of genomic outcomes, including gene duplication, recapture of genes lost through transfer to the nucleus, and chimaeric, half-monocot, half-dicot genes. These results imply the existence of mechanisms for the delivery of DNA between unrelated plants, indicate that horizontal transfer is also a force in plant nuclear genomes, and are discussed in the contexts of plant molecular phylogeny and genetically modified plants.     

Cell-matrix contact structures

Cell-extracellular matrix contacts are points on cell surfaces where adhesion receptors tether cells to matrix and are linked intracellularly to cytoskeletal components. These structures integrate cell organisation within tissues, support cell motility and specialised activities of differentiated cells, and transduce extracellular signals. Current characterisations of matrix contacts are based on morphological and biochemical criteria, yet the levels of definition of different contact types are very varied. Some contacts are surprisingly little-studied given their likely importance in vivo. Here, I describe the general features of matrix contacts, review the functions and molecular composition of major types of transient and stable matrix contacts, and discuss the information that is emerging on contact integration and dynamics in single cells. Received 7 September 2000; received after revision 4 October 2000; accepted 6 October 2000     

Maternal influences on cardiovascular pathophysiology.

Elevated blood pressure (BP) is of special clinical significance because of its association with pathophysiologies such as heart disease, renal failure, and stroke. We described the development of a protocol for use with hypertensive rats in which prepubertal exposure to a high salt (8% NaCl) diet results in a pathophysiological syndrome including rapid increase in BP, failure to maintain normal weight gain, renal damage, cerebrovascular lesions, and early mortality. These phenomena are described for the inbred spontaneously hypertensive rat (SHR), and for reciprocal F1 hybrids of a cross between SHR and the Dahl salt-sensitive (SS/Jr) inbred strain. The study with reciprocal F1s revealed striking effects of maternal environment on pathophysiological response to a high salt diet. F1s nurtured by SHR mothers weighed less at 35 days of age, and after exposure to the high salt diet suffered more rapid BP increases, greater incidence of stroke, body weight loss, and mortality, than F1s nurtured by SS/Jr dams. These results suggest that maternal mediation of the nutritional status of the animal may play an important role in determining susceptibility to elevated BP and subsequent pathophysiology associated with exposure to a high salt diet. The implication of these findings for human hypertension is briefly discussed.     

Intramembrane charge movement restored in dysgenic skeletal muscle by injection of dihydropyridine receptor cDNAs

The skeletal muscle dihydropyridine (DHP) receptor is essential in excitation-contraction (EC) coupling. The receptor is postulated to be the voltage sensor giving rise to the intramembrane current, termed charge movement. We have now tested this hypothesis using myotubes from mice with the muscular dysgenesis mutation, which alters the skeletal muscle DHP receptor gene and prevents its expression. Our results indicate that charge movement is deficient in dysgenic myotubes but is fully restored following injection of an expression plasmid carrying the rabbit skeletal muscle DHP receptor complementary DNA, strongly supporting the hypothesis that the DHP receptor is the voltage sensor for EC coupling in skeletal muscle. Additionally, our data obtained for normal and chimaeric DHP receptor constructs demonstrate that DHP receptors with widely differing abilities to function as calcium channels and to mediate EC coupling produce very similar charge movements.