Biomedical subjects

M L Lydrup

Publications and source records attributed to M L Lydrup.

5 recordsLinked to original sources

PubMed1992

Paradoxical decrease in cytosolic calcium with increasing depolarization by potassium in guinea-pig mesotubarium smooth muscle.

The free intracellular Ca2+ concentration ([Ca2+]i) was measured simultaneously with isometric force in strips of guinea-pig mesotubarium using the Fura-2 technique. [Ca2+]i and force were maximal at a relatively low (30 mM) concentration of extracellular K+ ([K+]o), and declined at 90 and 140 mM K+. Plateau values of both [Ca2+]i and force were higher in the presence of 5.10(-6) M ryanodine, indicating that the sarcoplasmic reticulum (SR) contributes to the decline with depolarization. Force and [Ca2+]i at 90 mM K+ were both lower then the high-K+ solution was applied after a period in 30 mM K+ than after a period in normal solution (5.9 mM K+), consistent with inactivation of Ca2+ channels during prolonged depolarization. Addition of carbachol to the depolarized muscle caused a maintained increase in force without maintained increase in [Ca2+]i. We conclude that the decrease in force at increased [K+]o (the "calcium-potassium paradox") is due to a membrane-potential-mediated decrease in [Ca2+]i and, to a lesser extent, to desensitization of the contractile-regulatory apparatus to Ca2+.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

PubMed1991

Metabolic correlates to pacemaker activity in the smooth muscle of guinea-pig mesotubarium.

Oxygen consumption (FO2) and lactate production (Flac) were measured during spontaneous activity in the guinea-pig mesotubarium. During spontaneous contractions FO2 increased to maximally 0.270 +/- 0.025 mumol min-1g-1 (n = 23), followed by a rapid fall immediately upon relaxation. In the relaxed period (5-15 min) between spontaneous contractions FO2 continued to slowly decrease by about 25% towards a final value of 0.150 +/- 0.01 mumol min-1g-1. Flac showed no consistent variation during the relaxed period. Ouabain (10(-6)M) produced a contracture, which was abolished by the Ca2(+)-antagonist felodipine (10(-6)M). In the presence of felodipine, addition of ouabain caused depolarization and a decrease of oxygen consumption by 21% and of lactate production by 31%. Exchange of glucose in the physiological Krebs solution for beta-hydroxybutyrate did not influence spontaneous activity, while subsequent addition of cyanide (2 mM) abolished contractions and caused a hyperpolarization of 15 mV. Blockade of ATP-dependent K+ channels by addition of glibenclamide (10(-7)M) to the relaxed muscle in this situation caused spontaneous contractile activity to reappear. In glucose-containing Krebs solution glibenclamide had no effect on the spontaneous contractile and electrical activity and contractions persisted after addition of cyanide. The relaxing and hyperpolarizing effect of pinacidil could be counteracted by addition of glibenclamide. The results suggest that a decrease in electrogenic Na+/K(+)-pump activity in the course of the relaxed period between contractions could contribute to the pacemaker behaviour. ATP-dependent K+ channels, while having little influence on the spontaneous contractile activity under normal metabolic conditions, could be activated during blockade of aerobic and anaerobic metabolism, leading to inhibition of pacemaker activity.

Adenosine Triphosphate↗

PubMed1991

Role of K+ channels in spontaneous electrical and mechanical activity of smooth muscle in the guinea-pig mesotubarium.

1. The spontaneous electrical and mechanical activity and the efflux rate of 86Rb+ in the guinea-pig mesotubarium were studied in the presence of agents interacting with K+ channels. 2. Tetraethylammonium (TEA, 10 mM) increased the amplitude of the action potentials while having no consistent effect on the frequency or amplitude of spontaneous contractions. 3. 4-Aminopyridine (4-AP, 1-5 mM) caused a graded increase in the duration of the contractions and of the electrical slow waves, and a decrease in the duration of the relaxed period between contractions. At 4 mM-4-AP or more the cell was unable to repolarize from the slow wave and the membrane depolarized to -26 mV from the normal resting potential of -63 mV. The rate of 86Rb+ efflux in the presence of 5 mM-4-AP was higher than that at 60 mM-K+, where the membrane potential is -24 mV. 4. 4-AP (5 mM) evoked a contracture in Ca(2+)-free solution, containing 1 mM-EGTA, both at the normal [K+]o of 5.9 mM and at 60 mM-K+, suggesting release of intracellular Ca2+. 5. Apamin (0.1-1 microM) and charybdotoxin (1-10 nM), blockers of Ca(2+)-dependent K+ channels, were without effects on the spontaneous electrical and mechanical activity. 6. The K+ channel opener pinacidil (10 microM) inhibited the spontaneous contractions and hyperpolarized the membrane by about 7 mV. The permeability to 86Rb+ was increased by a factor of 1.4. 7. It is concluded that different K+ channels are involved in the generation of spikes and slow waves: one sensitive to TEA and responsible for repolarization of the individual action potential, and another sensitive to 4-AP and responsible for repolarization of the slow wave. The duration of the relaxed period can be influenced by activation of K+ channels sensitive to pinacidil.

4-Aminopyridine↗

PubMed1990

Free cytosolic calcium during spontaneous contractions in smooth muscle of the guinea-pig mesotubarium.

The free intracellular calcium ion concentration ([Ca2+]i) was measured simultaneously with isometric force in strips of guinea-pig mesotubarium using the Fura-2 technique. During the relaxed period (5-15 min) between spontaneous contractions [Ca2+]i continues to decrease after full mechanical relaxation to reach a minimal level of 86 +/- 8 nM (n = 9) just before the start of the next contraction. During the spontaneous contractions (5-15 min) [Ca2+]i reached a maximum of 211 +/- 19 nM and then oscillated between 155 +/- 16 nM and 194 +/- 9 nM. Increased extracellular Ca2+ concentration to 10 mM from the standard concentration of 1.5 mM caused a decreased frequency of spontaneous contractions and an increase in [Ca2+]i both in the relaxed and contracted states. In 10 mM extracellular Ca2+, addition of AlF4-, as 1 mM NaF + 10 microM AlCl3, caused a sustained increase in [Ca2+]i and maintained force. Addition of verapamil (10 microM) in this situation decreased [Ca2+]i to the resting level. The results suggest that the cyclic appearance of trains of action potentials is related to variation in [Ca2+]i, possibly via inactivation of Ca2(+)-dependent K+ channels.

Action Potentials↗

PubMed1990

Effects of extracellular K+ and Ca2+ on membrane potential, contraction and 86Rb+ efflux in guinea-pig mesotubarium.

The effects of varying extracellular concentrations of K+ and Ca2+ [K+]o and [Ca2+]o on force development and membrane potential were investigated in the guinea-pig mesotubarium. At [K+]o up to 40 mM, spontaneous action potentials were present, while higher [K+]o gave sustained contractures at a stable membrane potential (-24 to -12 mV for [K+]o from 60 to 120 mM). Tension decreased successively with increasing [K+]o from 30 to 120 mM. The relaxing potency of the dihydropyridine Ca2+ antagonist, felodipine, increased as the membrane was depolarized with increasing [K+]o and action potentials ceased. These results are compatible with the existence of Ca2+ channels showing voltage-dependent affinity with dihydrophyridines. Increasing [Ca2+]o from 2.5 to 10 mM caused membrane hyperpolarization by about 11 mV and was accompanied by a lower frequency of spontaneous contractions and a longer duration of the relaxation between contractions. 86Rb+ efflux measurements in 60 mM K+ in the absence and presence of felodipine revealed a Ca2(+)-dependent component of the voltage-activated efflux. In normal solution (5.9 mM K+), efflux in the presence of felodipine was similar to the minimal value during normal spontaneous activity. The results indicate regulation of the permeability of K+ channels by the intracellular Ca2+ concentration ([Ca2+]i) and suggest participation of such channels in the generation of the regularly occurring bursts of action potentials characteristic of spontaneous activity in the mesotubarium.

Animals↗