Facilitatory effect of Ca2+ on the noradrenaline-evoked cation current in rabbit portal vein smooth muscle cells. 1998

R M Helliwell, and W A Large
Department of Pharmacology and Clinical Pharmacology, St George's Hospital Medical School, Cranmer Terrace, London SW17 0RE, UK.

1. The facilitatory effect of external calcium ions (Ca2+o) on the alpha1-adrenoceptor-activated non-selective cation current (Icat) was investigated in rabbit portal vein cells using noise and voltage-jump relaxation analysis of the whole-cell macroscopic current. 2. Micromolar concentrations of Ca2+o potentiated the peak amplitude of Icat at a holding potential (Vh) of -50 mV. The effective [Ca2+]o which produced a 50% potentiation (EC50) was 3 microM. 3. From noise analysis the estimated single channel conductance (gamma) was approximately 23 pS with [Ca2+]o between 3 and 100 microM, whereas in < 10 nM or 1 microM Ca2+o gamma was approximately 10 pS. 4. The spectral density function of Icat at negative potentials could be described by the sum of two Lorentzians in every [Ca2+]o examined. The time constant of the lower frequency Lorentzian component (tau1) was about 11 ms in < 10 nM Ca2+o and was about 45 ms in micromolar concentrations of Ca2+o (1-100 microM). In contrast, the time constant of the higher frequency component (tau2) was similar in < 10 nM Ca2+o and 100 microM Ca2+o (between 1 and 2 ms). 5. The lower frequency Lorentzian component was responsible for about half the total current variance in < 10 nM Ca2+o whereas in micromolar concentrations of Ca2+o it was responsible for most of the measured current variance. 6. In voltage-jump experiments, on stepping the voltage from -50 to +50 mV the instantaneous current was followed by an exponential decline of Icat. Stepping back to -30 mV produced an exponential inward relaxation (Irelax,-30 mV) leading to an increase in the steady-state amplitude of Icat in micromolar concentrations of Ca2+o, but this relaxation was not observed in < 10 nM Ca2+o. The relative amplitude of Irelax,-30 mV increased in an [Ca2+]o-dependent manner (EC50 was 2 microM) although the time constant of this relaxation (taurelax,-30 mV) remained unchanged (about 60 ms between 2 and 100 microM Ca2+o). 7. The data suggest that Ca2+o produces marked changes in the kinetics and single channel conductance of cation channels, which may account for the facilitatory effect of micromolar concentrations of Ca2+o on the peak amplitude of Icat.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008297 Male Males
D008564 Membrane Potentials The voltage differences across a membrane. For cellular membranes they are computed by subtracting the voltage measured outside the membrane from the voltage measured inside the membrane. They result from differences of inside versus outside concentration of potassium, sodium, chloride, and other ions across cells' or ORGANELLES membranes. For excitable cells, the resting membrane potentials range between -30 and -100 millivolts. Physical, chemical, or electrical stimuli can make a membrane potential more negative (hyperpolarization), or less negative (depolarization). Resting Potentials,Transmembrane Potentials,Delta Psi,Resting Membrane Potential,Transmembrane Electrical Potential Difference,Transmembrane Potential Difference,Difference, Transmembrane Potential,Differences, Transmembrane Potential,Membrane Potential,Membrane Potential, Resting,Membrane Potentials, Resting,Potential Difference, Transmembrane,Potential Differences, Transmembrane,Potential, Membrane,Potential, Resting,Potential, Transmembrane,Potentials, Membrane,Potentials, Resting,Potentials, Transmembrane,Resting Membrane Potentials,Resting Potential,Transmembrane Potential,Transmembrane Potential Differences
D009126 Muscle Relaxation That phase of a muscle twitch during which a muscle returns to a resting position. Muscle Relaxations,Relaxation, Muscle,Relaxations, Muscle
D009131 Muscle, Smooth, Vascular The nonstriated involuntary muscle tissue of blood vessels. Vascular Smooth Muscle,Muscle, Vascular Smooth,Muscles, Vascular Smooth,Smooth Muscle, Vascular,Smooth Muscles, Vascular,Vascular Smooth Muscles
D009638 Norepinephrine Precursor of epinephrine that is secreted by the ADRENAL MEDULLA and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the LOCUS CERULEUS. It is also found in plants and is used pharmacologically as a sympathomimetic. Levarterenol,Levonorepinephrine,Noradrenaline,Arterenol,Levonor,Levophed,Levophed Bitartrate,Noradrenaline Bitartrate,Noradrénaline tartrate renaudin,Norepinephrin d-Tartrate (1:1),Norepinephrine Bitartrate,Norepinephrine Hydrochloride,Norepinephrine Hydrochloride, (+)-Isomer,Norepinephrine Hydrochloride, (+,-)-Isomer,Norepinephrine d-Tartrate (1:1),Norepinephrine l-Tartrate (1:1),Norepinephrine l-Tartrate (1:1), (+,-)-Isomer,Norepinephrine l-Tartrate (1:1), Monohydrate,Norepinephrine l-Tartrate (1:1), Monohydrate, (+)-Isomer,Norepinephrine l-Tartrate (1:2),Norepinephrine l-Tartrate, (+)-Isomer,Norepinephrine, (+)-Isomer,Norepinephrine, (+,-)-Isomer
D011817 Rabbits A burrowing plant-eating mammal with hind limbs that are longer than its fore limbs. It belongs to the family Leporidae of the order Lagomorpha, and in contrast to hares, possesses 22 instead of 24 pairs of chromosomes. Belgian Hare,New Zealand Rabbit,New Zealand Rabbits,New Zealand White Rabbit,Rabbit,Rabbit, Domestic,Chinchilla Rabbits,NZW Rabbits,New Zealand White Rabbits,Oryctolagus cuniculus,Chinchilla Rabbit,Domestic Rabbit,Domestic Rabbits,Hare, Belgian,NZW Rabbit,Rabbit, Chinchilla,Rabbit, NZW,Rabbit, New Zealand,Rabbits, Chinchilla,Rabbits, Domestic,Rabbits, NZW,Rabbits, New Zealand,Zealand Rabbit, New,Zealand Rabbits, New,cuniculus, Oryctolagus
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D004558 Electric Stimulation Use of electric potential or currents to elicit biological responses. Stimulation, Electric,Electrical Stimulation,Electric Stimulations,Electrical Stimulations,Stimulation, Electrical,Stimulations, Electric,Stimulations, Electrical
D004594 Electrophysiology The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.

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