On the mechanism of ?-adrenergic regulation of the Ca channel in the guinea-pig heart

Kameyama, Masaki; Hofmann, Franz; Trautwein, W.

doi:10.1007/bf00582573

Cited by 377 publications

(177 citation statements)

References 46 publications

Supporting

Mentioning

160

Contrasting

Order By: Relevance

“…L-type Ca currents are often subject to extensive regulation./Ca L of TRCs might be directly under the control of a second messenger as, for instance, the betaadrenoreceptor pathway in cardiocytes (Kameyama et al, 1985;Pelzer et al, 1990). This possibility remained unexplored in this study.…”

Section: Two Types Of Ca Currentsmentioning

confidence: 49%

Membrane currents in taste cells of the rat fungiform papilla. Evidence for two types of Ca currents and inhibition of K currents by saccharin.

Béhé

DeSimone

Avenet

et al. 1990

The Journal of General Physiology

171

View full text Add to dashboard Cite

Taste buds were isolated from the fungiform papilla of the rat tongue and the receptor cells (TRCs) were patch clamped. Seals were obtained on the basolateral membrane of 281 TRCs, protruding from the intact taste buds or isolated by micro-dissection. In whole-cell configuration 72% of the cells had a TTX blockable transient Na inward current (mean peak amplitude 0.74 hA). All cells had outward K currents. Their activation was slower than for the Na current and a slow inactivation was also noticeable. The K currents were blocked by tetraethylammonium, Ba, and 4-aminopyridine, and were absent when the pipette contained Cs instead of K. With 100 mM Ba or 100 mM Ca in the bath, two types of inward current were observed. An L-type Ca current (ICaL) activated at -20 mV had a mean peak amplitude of 440 pA and inactivated very slowly. At 3 mM Ca the activation threshold of ICa L was near -40 mV. A transient T-type current (/CAT) activated at -50 mV had an average peak amplitude of 53 pA and inactivated with a time constant of 36 ms at -30 inV. ICR L was blocked more efficiently by Cd and D600 than/Ca T. ICa T was blocked by 0.2 mM Ni and half blocked by 200 #M amiloride. In whole-cell voltage clamp, Na-saccharin caused (in 34% of 55 cells tested) a decrease in outward K currents by 21%, which may be expected to depolarize the TRCs. Also, Na-saccharin caused some taste cells to fire action potentials (on-ceLl, 7 out of 24 cells; whole-ceLl, 2 out of 38 cells responding to saccharin) of amplitudes sufficient to activate/CAL. ThUS the action potentials will cause Ca inflow, which may trigger release of transmitter.

show abstract

Section: Two Types Of Ca Currentsmentioning

confidence: 49%

Membrane currents in taste cells of the rat fungiform papilla. Evidence for two types of Ca currents and inhibition of K currents by saccharin.

Béhé

DeSimone

Avenet

et al. 1990

The Journal of General Physiology

171

View full text Add to dashboard Cite

show abstract

“…For example, Kameyama, Hofmann, and Trautwein (1985) showed that the nonhydrolyzable ATP analogue, ATP~/S, introduced into guinea pig ventricular myocytes via the pipette, enhanced both basal and Iso-stimulated wholecell Ca z+ currents (Kameyama et al, 1985;Kameyama, Hescheler, Hofmann, and Trautwein, 1986;Hescheler, Kameyama, and Trautwein, 1987), and slowed (Kameyama et al, 1985) or prevented (Hescheler et al, 1987) the current decline after washing out Iso, results consistent with thiophosphorylation of Ca 2+ channels rendering them relatively resistant to the normally strong activity of endogenous phosphatases.…”

Section: Comparison With Pka Regulation Of Cardiac Ca E+ Currentsmentioning

confidence: 61%

Functionally distinct phospho-forms underlie incremental activation of protein kinase-regulated Cl- conductance in mammalian heart.

Hwang

Horie

Gadsby

1993

The Journal of General Physiology

107

View full text Add to dashboard Cite

The regulation of cardiac CI-conductance by cAMP-dependent protein kinase (PKA) and cellular phosphatases was studied in isolated guinea pig ventricular myocytes by using wide-tipped, perfused pipettes to record whole-cell currents. Exposure to forskolin (Fsk) or isoproterenol (Iso) elicits a CI-conductance that results exclusively from PKA-dependent phosphorylation because it can be completely abolished, or its activation fully prevented, by switching to pipette solution containing PKI, a synthetic peptide inhibitor of PKA. The CI-conductance activated by micromolar concentrations of either agonist reached its steady-state amplitude in 1-2 min and was deactivated promptly and entirely, usually within 2 min, upon washing out the agonist, implying a continuous high level of activity of endogenous protein phosphatases. Accordingly, intraceUular application of okadaic acid or microcystin, both potent inhibitors of protein phosphatases 1 and 2A, during exposure to Fsk enhanced the steady-state CI-conductance and slowed its deactivation after washing out the Fsk. Maximal potentiation of the conductance, by ~ 60%, was obtained with pipette concentrations of ~ 10 I~M okadaic acid (or ~ 5 ~tM microcystin) and did not result from an increase in the apparent affirfity for Fsk. In the presence of maximally effective concentrations of okadaic acid and/or microcystin, deactivation of the enhanced CI-conductance upon washout of agonist was incomplete, with about half of the conductance persisting indefinitely. That residual conductance did not reflect continued action of PKA because it was insensitive to PKI, but was identified as a fraction of the activated CI-conductance by its biophysical characteristics. The results suggest that complete deactivation of the PKA-regulated cardiac CI-conductance requires dephosphorylation by a type 1 and/or 2A phosphatase, but that partial deactivation can be accomplished by activity of some other phosphatase(s). These findings are' consistent with sequential phosphorylation of a protein, probably the CI-channel itself, at two different kinds

show abstract

“…These effects of HF are similar to those seen in the presence of dihydropyridine calcium channel agonists [9-121 and less similar to those seen following phosphorylation of the calcium channel [5,7,13]. Inactivation of Ica is thought to consist of both voltage-and calcium-dependent components [ 141.…”

Section: Discussionmentioning

confidence: 82%

An endogenous ‘hypertensive factor’ enhances the voltage‐dependent calcium current

et al. 1989

View full text Add to dashboard Cite

The effects of an immunoaffinity-purified putative endogenous hypertensive factor (HF) on voltage-dependent calcium current in frog cardiac myocytes were assessed. In 9 out of 10 cells, HF reversibly increased the peak amplitude of the calcium current. HF increased peak calcium current density at -5 mV from a control level of 1.8 & 1.3 pA/pF (mean & SD) to 4.4 + 2.0 pA/pF. HF shifted the peak of the calcium current-voltage relationship in the hyperpolarizing direction. HF shifted the voltage dependence of the inactivation of the calcium current to more negative potentials with prepulses from 40 to 0 mV, but the inactivation was not affected with prepulses more positive than 0 mV. Modulation of the voltagedependent calcium current by HF may be the mechanism underlying its pressor effects.

show abstract

On the mechanism of ?-adrenergic regulation of the Ca channel in the guinea-pig heart

Cited by 377 publications

References 46 publications

Membrane currents in taste cells of the rat fungiform papilla. Evidence for two types of Ca currents and inhibition of K currents by saccharin.

Membrane currents in taste cells of the rat fungiform papilla. Evidence for two types of Ca currents and inhibition of K currents by saccharin.

Functionally distinct phospho-forms underlie incremental activation of protein kinase-regulated Cl- conductance in mammalian heart.

An endogenous ‘hypertensive factor’ enhances the voltage‐dependent calcium current

Contact Info

Product

Resources

About