Biomedical subjects

D Feldmeyer

Publications and source records attributed to D Feldmeyer.

23 records · Page 2Linked to original sources

PubMed1990

Effects of gallopamil on calcium release and intramembrane charge movements in frog skeletal muscle fibres.

1. Intramembrane charge movements and changes in intracellular Ca2+ concentration were studied in voltage clamp experiments on cut twitch muscle fibres of the frog. The restoration from inactivation caused by steady depolarization and its modification by the phenylalkylamine Ca2+ channel antagonist gallopamil (D600, 10-30 microM) were investigated. 2. D600 prevented the restoration from inactivation of Ca2+ release which normally occurred at -80 mV. In D600 Ca2+ release recovered from inactivation at -120 mV. 3. D600 did not alter the characteristics of intramembrane charge movements in the depolarized fibre (charge 2) but the increase in the amount of mobile charge in the test voltage range above -60 mV, which normally occurs after changing the holding potential to -80 mV, was suppressed. The charge movement characteristics of D600-paralysed fibres, which were held at -80 mV, equalled those of normal depolarized and inactivated fibres. 4. Control records for the charge movement analysis were always obtained by voltage steps above 0 mV. Using the 'conventional' control in the potential range between -80 and -160 mV led to an underestimation and a kinetic deformation of charge movements in D600-treated fibres, which was due to various amounts of nonlinear charge in the control. 5. Like the restoration of Ca2+ release at -80 mV in normal fibres the recovery from paralysis at -120 mV in D600-treated fibres was accompanied by a significant increase in mobile charge in the potential range positive of -60 mV. Both Ca2+ release and charge movement at test potentials above -60 mV recovered with almost identical time course. 6. Restoration of Ca2+ release at a holding potential of -80 mV in normal fibres or at -120 mV in D600-treated fibres could not be clearly correlated to charge movement changes in the voltage range negative of -60 mV (charge 2). 7. Our results are consistent with a voltage-dependent inhibitory effect of D600 on the charge displacement that controls Ca2+ release from the sarcoplasmic reticulum but provide little evidence for a conversion of charge 2 into the charge that is involved in the control of Ca2+ release.

Action Potentials↗

PubMed1990

Fast gating kinetics of the slow Ca2+ current in cut skeletal muscle fibres of the frog.

1. Calcium currents and intramembrane charge movements were measured in cut twitch muscle fibres of the frog and the time course of activation of the current was studied using various conditioning pulse protocols. 2. When a conditioning activation was produced by a depolarizing pulse which ended before inactivation occurred, a subsequent depolarization led to a faster onset of activation, indicating that the system had not completely returned to the initial state during the interval between the two pulses. 3. The interval between conditioning and test pulse was varied at different subthreshold potentials to study the time course of restoring the steady-state conditions. Complete restoration required a waiting period of about 1 min at the holding potential of -80 mV due to a very slow process but partial recovery was reached within 100 ms. This initial recovery process was strongly voltage dependent and became considerably slower when the interval potential approached the threshold for current activation. 4. Stepping to a roughly 10 mV subthreshold potential without applying a conditioning activation caused no change in the time course of the current produced by a subsequent test depolarization. Depolarizing just to the current threshold caused a slowly progressing acceleration of test current activation. 5. The peak current-voltage relation in the fast gating regime caused by a conditioning activation coincided with the current-voltage relation measured under steady-state conditions, indicating not that a new channel population had become activated but that the same channels showed a different gating behaviour. 6. Intramembrane charge movements measured in 2 mM-Cd2+ and tested at potentials between -40 and +40 mV showed negligible changes when preceded by a strong depolarization. 7. We discuss several possible models which can explain the fact that the current is speeded up by a conditioning activation while the charge movements remain unchanged. It is possible that the fast voltage-dependent transition which becomes visible after conditioning pulses reflects a rapid conformational change of the Ca2+ channel molecule which also occurs during its normal gating mode but remains undetectable in terms of conductance. In view of the hypothesis that the Ca2+ channel molecule forms a voltage sensor for excitation-contraction coupling this fast transition could be coupled to the control of Ca2+ release from the sarcoplasmic reticulum.

Animals↗

PubMed1989

Effects of lanthanum on contractile inactivation and D600-induced paralysis in twitch muscle fibres of the frog.

The effects of the trivalent ion La upon force inactivation were investigated in voltage-clamped toe muscle fibres of the frog Rana temporaria. In the presence of La, the contracture plateau was remarkably lengthened and spontaneous relaxation which reflects force inactivation was reduced. Subsequent depolarizations led to a further decrease in the rate of relaxation, indicating that La slowed down force inactivation in a depolarization-dependent manner. Moreover, the development of paralysis in muscle fibres was also affected by La. In Ca-free solutions, paralysis was induced after a sequence of no more than three pulses to 0 mV; in the presence of D600 only one pulse was sufficient. Addition of La suppressed paralysis in Ca-free solutions and decelerated the action of D600. It is assumed that La alters the kinetics of force inactivation by binding to and replacing Ca at a site linked to a molecule in the T-tubular membrane which functions as voltage sensor in excitation-contraction (EC) coupling.

Animals↗

PubMed1988

Effects of guanidinium on EC coupling and tension generation in frog skeletal muscle.

The effect of the chaotropic cation guanidinium on tension generation was investigated in voltage-clamped intact and mechanically skinned muscle fibres of the frog. When sodium was replaced by guanidinium in the solution a 20-mV shift of the sigmoidal activation curve towards less negative potentials was recorded. A similar shift in the voltage dependence of mechanical inactivation did not occur. The plateau phase of contractures activated by long-lasting depolarizations was significantly shortened in the presence of 77.5 mM guanidinium. In a second set of experiments, charge displacement currents were measured using the cut fibre preparation. Apparently, guanidinium had no effect on the voltage dependence of intramembrane charge movement. On the other hand, this cation caused a distinct increase in the amount of charge necessary to reach the contraction threshold at rheobase voltage from 12.4nC microF-1 to 23.4nC microF-1. Experiments on skinned fibres containing an operating sarcoplasmic reticulum demonstrated that 5 mM guanidinium diminished caffeine-induced tension development and substantially delayed the onset of the contractile response. However, guanidinium did not impair calcium-induced tension development of the contractile apparatus. These results suggest that the inhibitory action of guanidinium on excitation-contraction coupling is due to a depression of calcium release from the sarcoplasmic reticulum.

Animals↗

PubMedDate not supplied

NMDA receptor diversity in the cerebellum: identification of subunits contributing to functional receptors.

Recent studies of N-methyl-D-aspartate (NMDA) receptors have led to the suggestion that there are two distinct classes of native NMDA receptors, identifiable from their single-channel conductance properties. 'High-conductance' openings arise from NR2A- or NR2B-containing receptors, and 'low-conductance' openings arise from NR2C- or NR2D-containing receptors. In addition, the low-conductance channels show reduced sensitivity to block by Mg2+. The readily identified cell types and simple architecture of the cerebellum make it an ideal model system in which to determine the contribution of specific subunits to functional NMDA receptors. Furthermore, mRNA for all of these four NR2 subunits are represented in this brain region. We have examined NMDA channels in Purkinje cells, deep cerebellar nuclei (DCN) neurons and Golgi cells. First we find that NR2D-containing NMDA receptors give rise to low-conductance openings in cell-attached recordings from Purkinje cells. The characteristic conductance of these events cannot, therefore, be ascribed to patch excision. Second, patches from some DCN neurons exhibit mixed populations of high- and low-conductance openings. Third, Golgi cells also exhibit a mixed population of high- and low-conductance NMDA receptor openings. The features of these low-conductance openings are consistent with the presence of NR2D-containing NMDA receptors, as suggested by in situ hybridization data. On the other hand the existence of high-conductance channels, with properties typical of NR2B-containing receptors, was not expected. Our results provide new evidence about the subunit composition of NMDA receptors in identified cerebellar cells, and suggest that examination of single-channel properties is a potentially powerful approach for determining the possible subunit composition of native NMDA receptors.

Animals↗