Phasic insulin dependent diabetes mellitus: manifestations and cellular mechanisms.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to S McFarlane.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Voltage-gated potassium (K) currents are important in controlling a neuron's excitability. We have shown previously (McFarlane and Cooper, 1992) that neonatal superior cervical ganglia (SCG) neurons express three voltage-gated K currents: a noninactivating delayed-rectifier type current (IK), a rapidly inactivating A-current (IAf), and a slowly inactivating A-current (IAs). When grown in culture for 4 weeks without other cell types, SCG neurons lose their expression of IAf and IAs, suggesting that an extrinsic factor(s) is involved in controlling the expression of these currents. In vivo, SCG neurons are surrounded by non-neuronal cells. Therefore, in this study we investigated whether the ganglionic non-neuronal cells provide a factor required for A-current expression. We show that postnatal day 1 (P1) SCG neurons continue to express IAf and IAs when cocultured with their ganglionic non-neuronal cells. Medium conditioned by ganglionic non-neuronal cells mimics the non-neuronal cell influence on IAf and IAs expression, suggesting that the effects of non-neuronal cells are mediated by way of a secreted factor. Ciliary neurotrophic factor, a factor present in peripheral non-neuronal cells, had similar effects to those of ganglionic cell-conditioned medium. Moreover, we find that the dependence of IAf on a non-neuronal cell factor is developmentally regulated; P14 neurons grown in culture without other cell types continue to express IAf. However, IAs on P14 neurons maintains its dependence on a factor from non-neuronal cells. Finally, in addition to extrinsic control of voltage-gated K currents, we suggest that SCG neurons use intrinsic mechanisms to coordinate their expression of IAf, IAs, and IK such that changes in one K current are compensated for by reciprocal changes in one or more of the other K currents.
1. We have investigated the developmental expression of three voltage-gated K currents on neonatal rat superior cervical ganglion (SCG) neurons in vivo and in culture: a rapidly inactivating current (IAf), a slowly inactivating current (IAs), and a noninactivating current (IK). 2. On postnatal day 1 neurons (P1), mean peak IAs is 67 +/- 4 (SE) pA/pF, peak IAf is 27 +/- 3 pA/pF, and IK is 14 +/- 3 pA/pF. Over the next wk, there is a switch in the expression of these currents: IAs drops by 40%, whereas IAf increases by greater than 100%; there is no change in IK. On P14 neurons, IAs is 38 +/- 2 pA/pF, IAf is 64 +/- 5 pA/pF, and IK is 12 +/- 1 pA/pF. 3. The change in expression of K currents on SCG neurons over the first 2 postnatal wk is unaffected by preganglionic innervation or by innervation of the targets. 4. To learn more about the factors that affect K current expression on these neurons, we grew SCG neurons in culture without other cell types for various times, and we measured the expression of IAf, IAs, and IK. In culture, the currents remained at their P1 levels for the first 4-7 days. Thereafter, both IAs and IAf decreased to low levels over a period of 2-3 wk. These results suggest that an epigenetic factor(s) is necessary for the expression of IAf and IAf in vivo and that this factor is missing in culture. 5. When IAs and IAf decreased on neurons in culture, we observed a compensatory increase in IK. After 4 wk in culture, IK is fourfold greater than on neurons in vivo. This result suggests that these neurons have intrinsic mechanisms that coordinate the expression of different voltage-gated K currents.
1. We have characterized three voltage-gated potassium currents on neonatal rat nodose neurons: a rapidly inactivating current (IAf), a slowly inactivating current (IAs), and a noninactivating current (IK). 2. Most neurons expressed all three currents. However, we found that a significant number of neurons had only one of the two A-currents. 3. IAf activates rapidly (tau = 1.0-1.5 ms at -10 mV) and inactivates in 10-30 ms. The activation and steady-state inactivation curves were fit with Boltzmann distributions of V' = -21, k = 12 mV and V' = -73, k = -8 mV, respectively. 4. IAs activates more slowly than IAf (tau = 5.4-9.2 ms at -10 mV) and inactivates with two components (150-300 ms; 1-3 s). The activation and inactivation curves are shifted approximately 20 mV more positive than those of IAf, with Boltzmann coefficients of V' = -2, k = 14 mV and V' = -51, k = -14 mV, respectively. 5. Of the three, IK activates most slowly (tau = 29.4-38.3 ms at -10 mV) and at more positive potentials than IAf or IAs (V' = 16, k = 12 mV). IK does not inactivate over tens of seconds. 6. In addition, we have identified the single channels that underlie IAf and IAs. These two channels, Af and As, have the same single-channel conductance, 22 pS, but different inactivation kinetics. 7. Furthermore, we show that there is an inverse relationship between the appearance of A-currents (IAf and IAs) and the appearance of IK, suggesting that these neurons coordinate the expression of these currents in their membranes.
Explore the source record for details and available documents.
During nitrogen starvation, cells of the yeast Saccharomyces cerevisiae increased threefold in number, and little ribonucleic acid (RNA) and protein were accumulated. Both RNA and protein were extensivley degraded during starvation, suggesting that intracellular macromolecules could supply most of the growth requirements. The types and proportions of stable RNA synthesized during nitrogen deprivation were characteristic of exponentially growing cells; however, the complement of proteins synthesized was different. We conclude that, once events in the deoxyribonucleic acid division cycle are initiated, cells can complete division with little dependence on continued net cell growth.
Neurons are polarized cells with an axon and a dendritic arbor extending from the soma. Although the molecular mechanisms underlying axon guidance are rapidly being elucidated, those that regulate the orientation, morphology, and elaboration of dendritic processes are largely unknown. Several recent papers address these issues, and propose a set of molecular strategies that control dendrite development. This review discusses these papers and what they reveal to us about how cell signaling orchestrates neuronal form and connectivity during development.