Search results for "Calcium Channel"

Opioid poorly-responsive cancer pain. Part 3. Clinical strategies to improve opioid responsiveness.

2001

Some pain syndromes may be difficult to treat due to a poor response to opioids. This situation demands a range of alternative measures, including the use of adjuvant drugs with independent effects, such as antidepressants, sodium channel-blocking agents, steroids and anti-inflammatory drugs (NSAIDs); drugs that reduce opioid side effects; and drugs that enhance analgesia produced by opioids, such as N-methyl-D-aspartate (NMDA) antagonists, calcium channel antagonists, and clonidine. Other approaches, including opioid trials, neural blockade when necessary, and psychological interventions, also may be useful.

Synaptopodin regulates denervation-induced homeostatic synaptic plasticity

2013

Synaptopodin (SP) is a marker and essential component of the spine apparatus (SA), an enigmatic cellular organelle composed of stacked smooth endoplasmic reticulum that has been linked to synaptic plasticity. However, SP/SA-mediated synaptic plasticity remains incompletely understood. To study the role of SP/SA in homeostatic synaptic plasticity we here used denervation-induced synaptic scaling of mouse dentate granule cells as a model system. This form of plasticity is of considerable interest in the context of neurological diseases that are associated with the loss of neurons and subsequent denervation of connected brain regions. In entorhino-hippocampal slice cultures prepared from SP-de…

Cardiovascular effects induced by rolipram, a selective cAMP phosphodiesterase inhibitor: Interaction with adrenergic and calcium affecting drugs

1990

Kinetics and state-dependent effects of verapamil on cardiac L-type calcium channels.

1996

The voltage dependence and the kinetics of block by verapamil of L-type calcium current (ICa) were investigated in ventricular myocytes from rat hearts using the whole-cell patch-clamp technique. ICa was elicited repetitively in response to depolarizing voltage pulses from -80 mV to 0 mV at different pulse intervals and durations. Verapamil reduced the magnitude of ICa in a frequency-dependent manner without tonic component. The time course of ICa remained unchanged suggesting that not open but inactivated channels were affected by the drug. The interaction of verapamil with inactivated channels was investigated by the application of twin pulses. In the presence of verapamil, the duration o…

Cytoprotective effect of NMDA receptor antagonists on prion protein (PrionSc)-induced toxicity in rat cortical cell cultures

1993

Rat cortical cells were incubated with the Scrapie prion protein, PrionSc. At concentrations of 3 ng/ml of PrionSc and higher, the viability of the cells decreased significantly after a 12-h incubation period. Simultaneously, the degree of DNA fragmentation increased. In control experiments with antibodies against PrionSc, PrionSc lost its deleterious effect on neurons. PrionSc did not affect the viability of astrocytes. Drugs known to block NMDA receptor channels, such as memantine (1-amino-3,5-dimethyl-adamantane) (Mem), its analogue 1-N-methylamino-3,5-dimethyl-adamantane as well as (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) prevented the effect of …

Bax inhibitor-1 is likely a pH-sensitive calcium leak channel, not a H+/Ca2+ exchanger.

2014

The endoplasmic reticulum (ER) plays a key role in the synthesis, folding, and sorting of proteins, and disturbances of this delicate system can cause cell death. The ER also serves as the major intracellular calcium (Ca(2+)) store, and release of Ca(2+) from this store controls diverse cellular functions. At the interface of both these functions of the ER is Bax inhibitor-1 (BI-1), an evolutionarily conserved multifunctional protein that mediates Ca(2+) efflux from the ER and protects against ER stress. Several mechanisms have been proposed to explain how BI-1 might mediate Ca(2+) efflux from the ER. Chang et al. present structural evidence that a bacterial homolog of BI-1, BsYetJ, is a pH…

Two distinct Ca2+ influx pathways activated by the bradykinin B2 receptor.

1996

The hormone-induced depletion of cellular Ca stores provides a signal for the Ca2+ influx into electrically non-excitable cells; however, the underlying molecular mechanisms remain elusive. Therefore, we analyzed bradykinin-activated Ca2+ influx into human foreskin fibroblast cells, HF-15, by fura-2 and 45Ca labeling to discriminate between Ca2+ influx into the fura-sensitive compartment and Ca uptake into fura-insensitive Ca stores. Bradykinin-activated CaZt influx into the fura-sensitive compartment was blocked by inhibitors of NO synthases. These inhibitors also suppressed bradykinin-activated increases in cGMP, indicating that the NO-dependent increase in cGMP is involved in the activat…

Therapeutic management of elderly hypertensives with concomitant ischaemic heart disease.

1992

CHARACTERISTICS OF ELDERLY HYPERTENSIVES: Hypertension is most prevalent in older patients and is associated with increasing morbidity and mortality with age. Elderly hypertensives often suffer from concomitant diseases, such as ischaemic heart disease, caused by age-induced modifications to the cardiovascular system, haemodynamic function and neurohormone activity. THERAPEUTIC MANAGEMENT: Therapeutic management of elderly hypertensives with concomitant ischaemic heart disease must take account of the pharmacodynamic and pharmacokinetic changes that occur in older subjects and drugs should be selected for their efficacy in both diseases. Since elderly subjects often metabolize drugs more sl…

Stable expression in HEK-293 cells of the rat alpha3/beta4 subtype of neuronal nicotinic acetylcholine receptor.

1996

The alpha3/beta4 subtype of neuronal nicotinic acetylcholine receptor (nAChR) was stably expressed in human embryonic kidney (HEK) 293 cells that co-expressed a voltage-gated Ca2+ channel. alpha3/beta4-nAChR-expressing clones were identified using the fura-2 Ca2+ imaging technique, and were further characterised by single-cell and whole-cell patch-clamp studies. Acetylcholine (ACh) induced fast activating currents which showed desensitisation and inward rectification. The conductance of the ACh-activated channel was 29 pS. The order of potency of the nicotinic agonists tested was cytisine approximately = nicotine > acetylcholine. The EC50 value for ACh was 145 microM; the Hill coefficient w…

Tetrandrine and Isotetrandrine, Two Bisbenzyltetrahydroisoquinoline Alkaloids from Menispermaceae, with Rat Uterine Smooth Muscle Relaxant Activity

1992

Abstract The effects of two bisbenzyltetrahydroisoquinoline alkaloids, 1S, 1′S tetrandrine and its isomer 1R, 1′S isotetrandrine, were investigated in rat isolated uterus in order to identify the mechanism of relaxant action and to study the influence of the absolute configuration on the activity of these alkaloids. Both inhibited the uterine contraction induced by high K+, acetylcholine and oxytocin. In Ca2+-free medium, isotetrandrine relaxed the sustained contraction induced by oxytocin but tetrandrine did not. The relaxant effects of the alkaloids may be due to blockade of calcium influx through specific channels. Tetrandrine and isotetrandrine modify the calcium channel in a nonreversi…