Biomedical subjects

J E Dallman

Publications and source records attributed to J E Dallman.

4 recordsLinked to original sources

PubMed2000

Action potential waveform voltage clamp shows significance of different Ca2+ channel types in developing ascidian muscle.

1. Early in development, ascidian muscle cells generate spontaneous, long-duration action potentials that are mediated by a high-threshold, inactivating Ca2+ current. This spontaneous activity is required for appropriate physiological development. 2. Mature muscle cells generate brief action potentials only in response to motor neuron input. The mature action potential is mediated by a high-threshold sustained Ca2+ current. 3. Action potentials recorded from these two stages were imposed as voltage-clamp commands on cells of the same and different stages from which they were recorded. This strategy allowed us to study how immature and mature Ca2+ currents are optimized to their particular functions. 4. Total Ca2+ entry during an action potential did not change during development. The developmental increase in Ca2+ current density exactly compensated for decreased spike duration. This compensation was a function purely of Ca2+ current density, not of the transition from immature to mature Ca2+ current types. 5. In immature cells, Ca2+ entry was spread out over the entire waveform of spontaneous activity, including the interspike voltage trajectory. This almost continuous Ca2+ entry may be important in triggering Ca2+-dependent developmental programmes, and is a function of the slightly more negative voltage dependence of the immature Ca2+ current. 6. In contrast, Ca2+ entry in mature cells was confined to the action potential itself, because of the slightly more positive voltage dependence of the mature Ca2+ current. This may be important in permitting rapid contraction-relaxation cycles during larval swimming. 7. The inactivation of the immature Ca2+ current serves to limit the frequency and burst duration of spontaneous activity. The sustained kinetics of the mature Ca2+ current permit high-frequency firing during larval swimming.

Action Potentials↗

PubMed1998

Spontaneous activity regulates calcium-dependent K+ current expression in developing ascidian muscle.

1. In embryonic ascidian muscle, outward K+ currents develop in two stages: the initial expression of a slowly activating, voltage-gated K+ current (IKv) near the time of neurulation is followed about 6 h later by a rapidly activating calcium-activated K+ current (IK(Ca)). During this 6 h interval, inward Ca2+ currents (ICa) appear and the inward rectifier (IK(IR)), the sole resting conductance, is transiently downregulated. These events predict a period of spontaneous activity. The following experiments were designed to test this prediction and to examine the relevance of spontaneous activity for muscle cell development. 2. By recording activity in cell-attached patches, we have found that muscle cells generate spontaneous action potentials during this 6 h window of time when IK(IR) is downregulated and outward K+ currents are slow. Action potentials occur at a mean frequency of 13.9 min-1.3. When activity is blocked by the transient application of the Ca2+ channel blocker Cd2+, IK(Ca) fails to develop. This disruption is specific for IK(Ca): IK(IR) and ICa develop normally in activity-blocked cells. Application of Cd2+ either before or after the window of activity has no effect. 4. The reappearance of IK(IR) and the development of IK(Ca) and the mature form of ICa are all prevented by transcription blockers, with a sensitive period corresponding to the period of activity. 5. These data show that, although the expression of three channel types depends on transcription during the period of spontaneous activity, only the development of IK(Ca) depends on activity.

Animals↗

PubMed1996

Co-ordinated modulation of Ca2+ and K+ currents during ascidian muscle development.

1. The development of Ca2+ and K+ currents was studied in ascidian muscle cells at twelve embryonic stages from gastrulation to the mature cell, a period of 24 h. A high degree of co-ordination occurs between the development of the inwardly rectifying K+ current (IK(IR)), which sets the resting potential, and Ca2+ and outward K+ currents, which determine action potential waveform. 2. At neurulation IK(IR), which had been present since fertilization, begins to decrease, reaching 12% of its previous density in 6 h. IK(IR) then immediately begins to increase again, reaching its previous density in another 6 h. 3. When IK(IR) begins to decrease, a high-threshold inactivating Ca2+ current and a slowly activating voltage-gated K+ current appear. 4. When IK(IR) returns to its previous density, two new currents appear: a sustained Ca2+ current with the same voltage dependence, but different conotoxin sensitivity than the inactivating Ca2+ current; and a Ca(2+)-dependent K+ current, which activates 8-10 times faster and at potentials 20-30 mV more negative than the voltage-dependent K+ current. 5. The transient downregulation of IK(IR) destabilizes the resting potential and causes spontaneous action potentials to occur. Because IK(IR) is absent when only a slowly activating high-threshold outward K+ current is present, these action potentials are long in duration. 6. The return of IK(IR) and the appearance of the rapidly activating Ca(2+)-dependent K+ current eventually terminate this activity. The action potentials of the mature cell occur only on stimulation, and are 10 times shorter in duration than those in the immature cell.

Action Potentials↗

PubMed1995

Comparison of ionic currents expressed in immature and mature muscle cells of an ascidian larva.

We have compared the voltage-gated ion channels present in larval ascidian muscle at two developmental stages: muscle precursor cells just after the terminal cell division and mature contractile muscle, 7-11 hr later. All precursor cells express a high-threshold transient Ca current and a slowly activating delayed K current, and about half the cells express a low-threshold transient Ca current. An inwardly rectifying K current, which had been present from fertilization until just before the terminal cell division, is absent. Mature muscle retains two of the tailbud currents: the low-threshold transient Ca current and the slow delayed K current, although at larger densities, and also expresses a high-threshold Ca current that is similar in most respects to the precursor cell current but that lacks inactivation. In addition, mature muscle expresses two rapidly activating outward K currents, one voltage and one Ca dependent, that generate a composite outward K current that is eight times larger and activates eight times faster than the tailbud K current. Mature muscle also reexpresses the inward rectifier. We propose that the transient absence of the inward rectifier and the slow activation of the delayed K current early in development create a window of developmental time when spontaneous electrical activity is likely.

Action Potentials↗