Blockade of K+ contractures in skeletal muscle by opioid drugs: a nonstereospecific effect

1989 ◽  
Vol 67 (5) ◽  
pp. 435-441
Author(s):  
Tushar G. Kokate ◽  
George B. Frank
Keyword(s):  
Skeletal Muscle ◽  
Calcium Channels ◽  
Opiate Receptors ◽  
Bathing Solution ◽  
Drug Concentrations ◽  
High K ◽  
Opioid Drugs ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
Sucrose Gap

The effect of several opioid drugs was tested on the K+ contractures in frog's skeletal muscle. These contractures are produced by the entrance of extracellular Ca2+ ions via the voltage-dependent, slow Ca2+ channels located in the T tubules. Morphine and other opioid agonists in concentrations ranging from 10−10 to 10−5 M inhibited K+ contractures. The stereoisomers, dextrorphan and levorphanol, were found to have identical potency in inhibiting high K+ contractures, suggesting that this was a nonstereospecific blockade of voltage-dependent calcium channels by the opioid drugs despite the low effective drug concentrations. In agreement with this conclusion it was found that the inhibition of K+ contractures by the opioids was not antagonized by naloxone. It also was observed using a sucrose gap apparatus that these opioid drugs in concentrations used to block the high K+ contractures did not reduce the K+-induced membrane depolarization. Raising the bathing solution Ca2+ concentration from 1.08 to 5 mM produced a reversal of the opioid-induced block of K+ contractures. Finally it was shown that while opioids completely blocked K+ contractures, they did not produce any effect on caffeine contractures showing that opioids do not deplete intracellular Ca2+ stores or inhibit the release of Ca2+ from intracellular sarcoplasmic reticulum stores. It was concluded that several opioid drugs in very low concentrations block K+ contractures in frog's skeletal muscle by a nonstereospecific block of voltage-dependent slow calcium channels.Key words: opioids, calcium channels, contractures, skeletal muscle, opiate receptors, narcotics.

scholarly journals Single calcium channel behavior in native skeletal muscle.

1995 ◽  
Vol 105 (2) ◽  
pp. 227-247 ◽  
Author(s):  
R T Dirksen ◽  
K G Beam
Keyword(s):  
Skeletal Muscle ◽  
Calcium Channels ◽  
Single Channel ◽  
Bay K 8644 ◽  
Dependent Manner ◽  
Channel Conductance ◽  
Single Channel Conductance ◽  
Whole Cell ◽  
Macroscopic Properties ◽  
Voltage Dependent

The purpose of this study was to use whole-cell and cell-attached patches of cultured skeletal muscle myotubes to study the macroscopic and unitary behavior of voltage-dependent calcium channels under similar conditions. With 110 mM BaCl2 as the charge carrier, two types of calcium channels with markedly different single-channel and macroscopic properties were found. One class was DHP-insensitive, had a single-channel conductance of approximately 9 pS, yielded ensembles that displayed an activation threshold near -40 mV, and activated and inactivated rapidly in a voltage-dependent manner (T current). The second class could only be well resolved in the presence of the DHP agonist Bay K 8644 (5 microM) and had a single-channel conductance of approximately 14 pS (L current). The 14-pS channel produced ensembles exhibiting a threshold of approximately -10 mV that activated slowly (tau act approximately 20 ms) and displayed little inactivation. Moreover, the DHP antagonist, (+)-PN 200-110 (10 microM), greatly increased the percentage of null sweeps seen with the 14-pS channel. The open probability versus voltage relationship of the 14-pS channel was fitted by a Boltzmann distribution with a VP0.5 = 6.2 mV and kp = 5.3 mV. L current recorded from whole-cell experiments in the presence of 110 mM BaCl2 + 5 microM Bay K 8644 displayed similar time- and voltage-dependent properties as ensembles of the 14-pS channel. Thus, these data are the first comparison under similar conditions of the single-channel and macroscopic properties of T current and L current in native skeletal muscle, and identify the 9- and 14-pS channels as the single-channel correlates of T current and L current, respectively.

Basolateral K+ conductance in principal cells of rat CCD

2005 ◽  
Vol 288 (3) ◽  
pp. F493-F504 ◽  
Author(s):  
Daniel A. Gray ◽  
Gustavo Frindt ◽  
Yu-Yang Zhang ◽  
Lawrence G. Palmer
Keyword(s):  
Single Channel ◽  
Outward Current ◽  
Whole Cell ◽  
Principal Cells ◽  
Luminal Membrane ◽  
High K ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
Cell Current ◽  
Single Channel Currents

Whole cell K+ current was measured by forming seals on the luminal membrane of principal cells in split-open rat cortical collecting ducts. The mean inward, Ba2+-sensitive conductance, with 40 mM extracellular K+, was 76 ± 12 and 141 ± 22 nS/cell for animals on control and high-K+ diets, respectively. The apical contribution to this was estimated to be 3 and 16 nS/cell on control and high-K+ diets, respectively. To isolate the basolateral component of whole cell current, we blocked ROMK channels with either tertiapin-Q or intracellular acidification to pH 6.6. The current was weakly inward rectifying when bath K+ was ≥40 mM but became more strongly rectified when bath K+ was lowered into the physiological range. Including 1 mM spermine in the pipette moderately increased rectification, but most of the outward current remained. The K+ current did not require intracellular Ca2+ and was not inhibited by 3 mM ATP in the pipette. The negative log of the acidic dissociation constant (p Ka) was ∼6.5. Block by extracellular Ba2+ was voltage dependent with apparent Ki at −40 and −80 mV of ∼160 and ∼80 μM, respectively. The conductance was TEA insensitive. Substitution of Rb+ or NH4+ for K+ led to permeability ratios of 0.65 ± 0.07 and 0.15 ± 0.02 and inward conductance ratios of 0.17 ± 0.03 and 0.57 ± 0.09, respectively. Analysis of Ba2+-induced noise, with 40 mM extracellular K+, yielded single-channel currents of 0.39 ± 0.04 and −0.28 ± 0.04 pA at voltages of 0 and −40 mV, respectively, and a single-channel conductance of 17 ± 1 pS.

Calmodulin interactions with IQ peptides from voltage-dependent calcium channels

2005 ◽  
Vol 288 (3) ◽  
pp. C669-C676 ◽  
Author(s):  
D. J. Black ◽  
D. Brent Halling ◽  
David V. Mandich ◽  
Steen E. Pedersen ◽  
Ruth A. Altschuld ◽  
...  
Keyword(s):  
Calcium Channels ◽  
The Other ◽  
Multiple Functions ◽  
Iq Motif ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
Voltage Dependent Calcium Channels ◽  
Cam Regulation

Calmodulin (CaM) functions as a Ca2+ sensor for inactivation and, in some cases, facilitation of a variety of voltage-dependent Ca2+ channels. A crucial determinant for CaM binding to these channels is the IQ motif in the COOH-terminal tail of the channel-forming subunit. The binding of CaM to IQ peptides from Lc-, P/Q-, and R-type, but not N-type, voltage-dependent Ca2+ channels increases the Ca2+ affinity of both lobes of CaM, producing similar N- and C-lobe Ca2+ affinities. Ca2+ associates with and dissociates from the N-lobe much more rapidly than the C-lobe when CaM is bound to the IQ peptides. Compared with the other IQ peptides, CaM-bound Lc-IQ has the highest Ca2+ affinity and the most rapid rates of Ca2+ association at both lobes, which is likely to make Ca2+ binding to CaM, bound to this channel, less sensitive than other channels to intracellular Ca2+ buffers. These kinetic differences in Ca2+ binding to the lobes of CaM when bound to the different IQ motifs may explain both the ability of CaM to perform multiple functions in these channels and the differences in CaM regulation of the different voltage-dependent Ca2+ channels.

Modulation by endogenously released ATP and opioids of chromaffin cell calcium channels in mouse adrenal slices

2011 ◽  
Vol 300 (3) ◽  
pp. C610-C623 ◽  
Author(s):  
A. Hernández ◽  
P. Segura-Chama ◽  
N. Jiménez ◽  
A. G. García ◽  
J. M. Hernández-Guijo ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Chromaffin Cells ◽  
Opiate Receptors ◽  
Tonic Inhibition ◽  
Inactivation Kinetics ◽  
High Threshold ◽  
Patch Clamp Technique ◽  
Whole Cell ◽  
Voltage Dependent ◽  
Patch Configuration

Modulation of high-threshold voltage-dependent calcium channels by neurotransmitters has been the subject of numerous studies in cultures of neurons and chromaffin cells. However, no studies on such modulation exist in chromaffin cells in their natural environment, the intact adrenal medullary tissue. Here we performed such a study in voltage-clamped chromaffin cells of freshly prepared mouse adrenal slices under the whole cell configuration of the patch-clamp technique. The subcomponents of the whole cell inward Ca2+ current ( ICa) accounted for 49% for L-, 28% for N-, and 36% for P/Q-type channels. T-type Ca2+ channels or residual R-type Ca2+ currents were not seen. However, under the perforated-patch configuration, 20% of ICa accounted for a toxin-resistant R-type Ca2+ current. Exogenously applied ATP and methionine-enkephalin (Met-enk) inhibited ICa by 33%. Stop-flow and Ca2+ replacement by Ba2+, which favored the release of endogenous ATP and opioids, also inhibited ICa, with no changes in activation or inactivation kinetics. This inhibition was partially voltage independent and insensitive to prepulse facilitation. Furthermore, in about half of the cells, suramin and naloxone augmented ICa in the absence of exogenous application of ATP/Met-enk. No additional modulation of ICa was obtained after bath application of exogenous ATP and opioids to these already inhibited cells. Augmentation of ICa was also seen upon intracellular dialysis of guanosine 5′-[β-thio]diphosphate (GDPβS), indicating the existence in the intact slice of a tonic inhibition of ICa in resting conditions. These results suggest that in the intact adrenal tissue a tonic inhibition of ICa exists, mediated by purinergic and opiate receptors.

Mechanism and role of high-potassium-induced reduction of intracellular Ca2+ concentration in rat osteoclasts

2003 ◽  
Vol 285 (2) ◽  
pp. C457-C466 ◽  
Author(s):  
Hiroshi Kajiya ◽  
Fujio Okamoto ◽  
Hidefumi Fukushima ◽  
Keisuke Takada ◽  
Koji Okabe
Keyword(s):  
Dependent Manner ◽  
Patch Clamp Technique ◽  
High Potassium ◽  
Entry Pathway ◽  
Pit Formation ◽  
Motile Cells ◽  
High K ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
Actin Rings

Osteoclasts are multinucleated, bone-resorbing cells that show structural and functional differences between the resorbing and nonresorbing (motile) states during the bone resorption cycle. In the present study, we measured intracellular Ca2+ concentration ([Ca2+]i) in nonresorbing vs. resorbing rat osteoclasts. Basal [Ca2+]i in osteoclasts possessing pseudopodia (nonresorbing/motile state) was around 110 nM and significantly higher than that in actin ring-forming osteoclasts (resorbing state, around 50 nM). In nonresorbing/motile osteoclasts, exposure to high K+ reduced [Ca2+]i, whereas high K+ increased [Ca2+]i in resorbing state osteoclasts. In nonresorbing/motile cells, membrane depolarization and hyperpolarization applied by the patch-clamp technique decreased and increased [Ca2+]i, respectively. Removal of extracellular Ca2+ or application of 300 μM La3+ reduced [Ca2+]i to ∼50 nM in nonresorbing/motile osteoclasts, and high-K+-induced reduction of [Ca2+]i could not be observed under these conditions. Neither inhibition of intracellular Ca2+ stores or plasma membrane Ca2+ pumps nor blocking of L- and N-type Ca2+ channels significantly reduced [Ca2+]i. Exposure to high K+ inhibited the motility of nonresorbing osteoclasts and reduced the number of actin rings and pit formation in resorbing osteoclasts. These results indicate that in nonresorbing/motile osteoclasts, a La3+-sensitive Ca2+ entry pathway is continuously active under resting conditions, keeping [Ca2+]i high. Changes in membrane potential regulate osteoclastic motility by controlling the net amount of Ca2+ entry in a “reversed” voltage-dependent manner, i.e., depolarization decreases and hyperpolarization increases [Ca2+]i.

Voltage-dependent calcium fluxes in skeletal muscle transverse tubule membranes in the range of late afterpotentials

1993 ◽  
Vol 71 (7) ◽  
pp. 518-521 ◽  
Author(s):  
A. Murat Öz ◽  
George B. Frank ◽  
Susan M. J. Dunn
Keyword(s):  
Skeletal Muscle ◽  
Calcium Channels ◽  
Resting State ◽  
Membrane Vesicles ◽  
Calcium Flux ◽  
Channel Blockers ◽  
Transverse Tubule ◽  
Voltage Dependent ◽  
Intact Muscle ◽  
Voltage Dependent Calcium Channels

Calcium flux responses mediated by voltage-dependent calcium channels have been studied in transverse tubule membrane vesicles from rabbit skeletal muscle. Vesicles were loaded with 45Ca2+, and membrane potentials were generated by establishing potassium gradients across the membrane in the presence of valinomycin. After the membranes were polarized to an estimated −80 mV to approximate the resting state of the cell, a significant 45Ca2+ efflux occurred upon subsequent depolarization to −60 mV. The efflux response was modulated by activators and inhibitors of slow, dihydropyridine-sensitive calcium channels, being inhibited by inorganic calcium channel blockers, verapamil, nifedipine, and (−)-SDZ 202 – 791 and potentiated by the dihydropyridine agonists (±)-Bay K8644 and (+)-SDZ 202 – 791. These results demonstrate that calcium channels in transverse tubule membranes can open to mediate calcium flux in the same range of membrane potential as the late afterpotentials that occur during tetanic contractions of intact muscle fibres.Key words: Ca2+ channels, dihydropyridines, skeletal muscle (rabbit), 45Ca2+ flux, late afterpotentials.

Sign in / Sign up

Export Citation Format

Share Document