Effect of dihydropyridines on calcium channels in isolated smooth muscle cells from rat vena cava

Mironneau, Jean; Yamamoto, Tatsuo; Sayet, I.; Arnaudeau, Serge; Rakotoarisoa, Lala; Mironneau, C.

doi:10.1111/j.1476-5381.1992.tb14253.x

Cited by 18 publications

(13 citation statements)

References 38 publications

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“…Voltage-gated Na + channels have been shown to be present in several different smooth muscle preparations including both vascular [13, 14, 15, 16, 17, 18, 19]and nonvascular types [20, 21, 22]. Of these previous reports, however, only one employed a tonic type of arterial myocytes (i.e., one not exhibiting action potentials) from the rabbit pulmonary artery [13].…”

Section: Discussionmentioning

confidence: 98%

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Voltage-Gated Sodium Channels in Human Aortic Smooth Muscle Cells

Cox¹,

Zhou²,

Tulenko³

1998

J Vasc Res

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Whole-cell, voltage clamp methods were used to study inward currents in human aortic smooth muscle cells in culture. Cells were plated on glass coverslips, cultured in supplemented M-199 media with 5% serum and studied as primary cells and at passages 2–5. Inward currents were measured with a pipette solution containing Cs⁺ and TEA⁺ to block K⁺ currents and with 2.5 mM [Ca²⁺]₀ in the perfusate. Inward currents activated at about –50 mV, peaked at about –15 mV and reversed at about +30 mV. Values of peak inward current averaged 14.7 ± 3.3 pA/pF and cell capacitance averaged 124 ± 10 pF (n = 35). These currents activated rapidly with a time-to-peak current of 2.4 ± 0.3 ms at a test potential of –10 mV from a holding potential of –80 mV. The current also inactivated rapidly with a time course that could be described by two components with time constants of 1.8 ± 0.2 and 17.8 ± 3.5 ms at –10 mV. The currents decreased when extracellular Na⁺ was reduced and were completely inhibited by 50 nM tetrodotoxin (TTX), suggesting that they represented voltage-gated Na⁺ currents (I_Na). Activation curves were characterized with a V_0.5 = –16.6 ± 2.4 mV and a slope factor k = –5.2 ± 0.2 mV while inactivation curves were characterized with a V_0.5 = –60.9 ± 1.7 mV and a slope factor k = 8.8 ± 0.4 mV. Lowering external [Ca²⁺] to zero increased the maximum I_Na, shifted its voltage dependence in the hyperpolarizing direction and increased the rate of I_Na inactivation. Increasing external [Ca²⁺] or [Mg²⁺]decreased I_Na and slowed its rate of inactivation. These studies demonstrate the presence of voltage-gated Na⁺ channels with high TTX sensitivity that are modulated by extracellular divalent cations in human aortic smooth muscle cells maintained in cell culture. Window currents were found in the voltage range of –50 to –20 mV, suggesting that these channels could contribute to the resting membrane potential.

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Section: Discussionmentioning

confidence: 98%

“…On the other hand, voltage-dependent Na + channels appear to be rarely expressed in tonic smooth muscle such as in arterial myocytes [13, 14, 15], but are more frequently found in phasic smooth muscle such as venous myocytes [16, 17, 18, 19]as well as in nonvascular smooth muscle cells [20, 21, 22]. …”

Section: Introductionmentioning

confidence: 99%

Voltage-Gated Sodium Channels in Human Aortic Smooth Muscle Cells

Cox¹,

Zhou²,

Tulenko³

1998

J Vasc Res

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“…This approach is validated by the fact that the KI values hence derived are usually comparable to the high affinity KD values obtained from binding experiments (Bean, 1984;Hamilton et al 1987;Mironneau, Yamamoto, Sayet, Arnaudeau, Rakotoarisoa & Mironneau, 1992; but see Hamilton et al 1987;Kunze et al 1987 (Hering, Beech, Bolton & Lim, 1988;Hering, Hughes, Timin & Bolton, 1993) or flashinduced competition techniques (Bechem & Hoffmann, 1993) to examine the effect of various DHPs on Ica-In these experiments, the environment of the Ca2+ channels could be changed within a few milliseconds at any given time during the depolarization or repolarization of the membrane potential, and k1 or k-, could be measured in separate protocols. However, to our knowledge, it remains unknown how these parameters are affected by membrane potential.…”

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confidence: 87%

“…resting vs. inactivated. Indeed, there seems to be a better agreement between functional IC50 values measured at depolarized potentials (-30 mV), which favour the inactivated states, and binding KD values for a number of DHP antagonists, such as (+)-Bay K 8644 (13 vs. 26 nM; Hamilton et al 1987), (-)-202 791 (1 vs. 0-9 nM; Hamilton et al 1987), isradipine (Lee et al 1987;Cognard et al 1986;Mironneau et al 1992; but see Hamilton et al 1987;Kunze et al 1987), and nitrendipine (Bean, 1984). An additional complexity comes from the fact that DHPs may bind to more than one binding site on the Ca2+ channel.…”

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confidence: 99%

Binding constants determined from Ca2+ current responses to rapid applications and washouts of nifedipine in frog cardiac myocytes.

Méry¹,

Hove‐Madsen²,

Mazet³

et al. 1996

The Journal of Physiology

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1. A fast perfusion system was used to analyse the kinetics of the response of L-type calcium current (Ica) to rapid applications and washouts of the dihydropyridine antagonist nifedipine in whole-cell patch-clamped frog ventricular myocytes.2. Both the inhibition of Ica induced by nifedipine and the recovery from inhibition upon washout of the drug behaved as mono-exponential functions of time.3. During application or washout of 100 nm nifedipine, only the peak amplitude of Ica varied but not its time course of activation or inactivation.4. The rate constant of the onset of Ica inhibition increased with the concentration of nifedipine. However, the time course of the recovery from inhibition was independent of drug concentration. 5. Both rate constants were strongly sensitive to the holding potential but insensitive to the test potential. 6. Using simple rate equations and a one-binding-site analysis it was possible to determine the rate constants for associaton (kl)

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“…The identification of functional voltage-gated Na + channels in quiescent and proliferating vascular smooth muscle cells (VSMC), however, has not been as forthcoming. Currently, I Na have been measured in smooth muscle cells isolated from the coronary artery, aorta, vena cava, and pulmonary artery of various species, including humans [5,16,23,27]. On only rare occasions have I Na been recorded in freshly dissociated human VSMC, although they are readily detected when the same cells are cultured [28].…”

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confidence: 99%

Identification of functional voltage-gated Na+ channels in cultured human pulmonary artery smooth muscle cells

Platoshyn

Remillard

Fantozzi

et al. 2005

Pflugers Arch - Eur J Physiol

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Electrical excitability, which plays an important role in excitation-contraction coupling in the pulmonary vasculature, is regulated by transmembrane ion flux in pulmonary artery smooth muscle cells (PASMC). This study aimed to characterize the electrophysiological properties and molecular identities of voltage-gated Na + channels in cultured human PASMC. We recorded tetrodotoxinsensitive and rapidly inactivating Na + currents with properties similar to those described in cardiac myocytes. Using RT-PCR, we detected transcripts of seven Na + channel α genes (SCN2A, 3A, 4A, 7A, 8A, 9A, and 11A), and two β subunit genes (SCN1B and 2B). Our results demonstrate that human PASMC express TTX-sensitive voltage-gated Na + channels. Their physiological functions remain unresolved, although our data suggest that Na + channel activity does not directly influence membrane potential, intracellular Ca 2+ release, or proliferation in normal human PASMC. Whether their expression and/or activity are heightened in the pathological state is discussed.Keywords membrane potential; Na + channels; vascular smooth muscle; pulmonary Voltage-gated Na + channels play a major role in regulating cell excitability, particularly as it pertains to the generation of action potentials in neurons, skeletal muscle, and cardiac myocytes. Evidence has shown that, in vascular smooth muscle, action potentials are not dependent on Na + channels since tetrodotoxin (TTX) has no effect on amplitude and duration of action potentials [18], leading to the belief that these channels might not be present or prominent in these tissues. Nonetheless, Na + currents (I Na ) have been measured in visceral smooth muscles such as myometrium and uterus (pregnant), colon, esophagus, stomach, and ureter as well as in certain vascular smooth muscles such as the portal and azygos veins [2,8,[24][25][26]31,33,34]. The identification of functional voltage-gated Na + channels in quiescent and proliferating vascular smooth muscle cells (VSMC), however, has not been as forthcoming. Currently, I Na have been measured in smooth muscle cells isolated from the coronary artery, aorta, vena cava, and pulmonary artery of various species, including humans [5,16,23,27]. On only rare occasions have I Na been recorded in freshly dissociated human VSMC, although they are readily detected when the same cells are cultured [28]. In isolated cases, I Na have been recorded in both freshly dispersed rabbit [27] de-differentiation and proliferation [28]. More specifically, voltage-gated Na + channel expression and activity may be required either to facilitate the transition or to promote the de-differentiation of cells from "contractile" to "synthetic" or "proliferative" phenotypes [20,30]. This raises the possibility that the expression of functional voltage-gated Na + channels in cultured cells act as a trigger for cell de-differentiation and proliferation, possibly via enhanced cytoplasmic free Ca 2+ concentration ([Ca 2+ ] cyt ).The molecular identification of the subunits that make ...

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Effect of dihydropyridines on calcium channels in isolated smooth muscle cells from rat vena cava

Cited by 18 publications

References 38 publications

Voltage-Gated Sodium Channels in Human Aortic Smooth Muscle Cells

Voltage-Gated Sodium Channels in Human Aortic Smooth Muscle Cells

Binding constants determined from Ca2+ current responses to rapid applications and washouts of nifedipine in frog cardiac myocytes.

Identification of functional voltage-gated Na+ channels in cultured human pulmonary artery smooth muscle cells

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