Activation Of Electrogenic Na Pump Research Articles

Possible involvement of sodium pump in the relaxation of rat aorta induced by alpha-human atrial natriuretic polypeptide.

In order to clarify whether the sodium handling of smooth muscle is associated with the relaxing action of alpha-human atrial natriuretic polypeptide (alpha-hANP), we examined the sodium pump-related effects of alpha-hANP on rat aortic smooth muscles. Application of Ca2+ (1.0 to 10.0 mM) to the muscle preincubated in Ca2+-free, and K+-free or 0.5 mM K+ medium for 60 min induced a contraction. Pretreatment with alpha-hANP (1 x 10(-8) M) decreased the contraction evoked in 0.5 mM [K+]o but not that in K+-free medium. After a contraction was elicited by norepinephrine in K+-free solution, an addition of KCl (1.4-5.4 mM) caused a transient relaxation in a concentration-dependent manner, presumably due to the activation of electrogenic Na pump. The alpha-hANP enhanced the relaxation, which was sensitive to ouabain, and the potentiation by alpha-hANP was inversely related to the concentration of K+ added. When alpha-hANP was applied to relax the muscle precontracted by norepinephrine in the varied concentration of external K+, alpha-hANP-induced relaxation was greater in 1.4 or 2.7 mM [K+]o than in 0 or 5.4 mM [K+]o. These results suggest that the vasodilating effect of alpha-hANP is at least partially mediated by the activation of electrogenic Na, K-pump and this effect is prominent when the Na, K-pump is partially suppressed.

Possibility of metabolic control of membrane excitation.

In the guinea pig taenia coli, when glycogen is depleted by repeating Ca-induced contracture in excess K solution containing no glucose, the tension cannot be maintained. The decrease in tension is accompanied by reduction of high energy phosphate compounds and oxygen consumption. When substrate is readmitted to the glycogen-depleted preparation in the presence of 2.4 mM Ca and 20 mM K, the first response is hyperpolarization of the membrane and relaxation, and this is followed by depolarization and development of contracture. The latter response is blocked by verapamil, suggesting that energy supply increases the Ca conductance of the plasma membrane. The early response is considered to be due to activation of electrogenic Ca pump, since this is not affected by ouabain as well as removal of Na and K. ATP produced by substrate readmission is probably preferentially utilized for Ca pump activation to reduce the intracellular Ca. The recovery of tension is likely to be brought about by ATP supply not only to the contractile machinery but also to the plasma membrane to remove inactivation of Ca conductance. It is postulated that as the energy source is depleted, energy consumption is automatically limited by suppressing Ca influx, as a self-defence mechanism. Since beta HB is as effective as glucose in the recovery of these processes, and also in the activation of electrogenic Na pump, the metabolic pathway of oxidative phosphorylation alone can support these functions without a contribution of the glycolytic pathway.

Hyperpolarization of mammalian skeletal muscle fibers in K-free media.

Time course of changes in resting potential following removal of K ions from Krebs solution was studied in the isolated rat soleus muscle. In K+-free Krebs solution the muscle fibers hyperpolarized to a peak within 60 min followed by a variable, gradual depolarization over the next few hours. A significant decrease of the intracellular K+ concentration ([K]i) occurred within 30 min in K+-free Krebs. Compensatory increase of the intracellular Na+ concentration ([Na]i) lagged behind [K]i change. Both hyperpolarization and successive depolarization were modified in K+-free medium containing different [Na]o, [Ca]o, or osmotic strength. A part of the hyperpolarization was reduced by adding ouabain. Therefore, ouabain-sensitive potential of the fibers in K+-free medium was attributed to the activation of electrogenic Na pump by K+ leaked out continuously from the fibers and accumulated just outside of cell membranes but not to changes of membrane Na+ and Cl- permeabilities. It is concluded that hyperpolarization of muscles exposed to K+-free medium is the sum of the diffusional K+ potential and ouabain-sensitive metabolic potential. Interestingly, the time course of changes of membrane response to K+-free krebs was identical for contralateral soleus muscles in the same rat, though it varied among different rats.

The electrogenic sodium pump and conductance changes in the post-tetanic hyperpolarization of crayfish median giant axons.

The mechanism of post-tetanic hyperpolarization (PTH) occurrence was investigated using the intracellar recording technique. The median giant axon of a crayfish abdominal nerve cord was repetitively stimulated to elicit PTH. When the membrane potential was hyperpolarized by intracellularly applied currents, PTH reversed its sign. K+ removal from the external medium increased the size of PTH and shifted its reversal potential in the hyperpolarizing direction. This results shows that an increase in K+ conductance contributes to the formation of PTH. In a K+-free medium, the size of PTH was reduced by replacement of Na+ with Li+ in the external medium, by application of ouabain or DNP, or by cooling. These procedures shifted the reversal potential in the depolarizing direction. These findings are interpreted as showing that, with K+ absent, PTH is partly due to the activity of electrogenic Na pump. With lowering of external Na+ concentration, PTH became larger and the reversal potential moved in the hyperpolarizing direction. The experiment suggests that Na+ conductance is also increased when PTH is elicited because one expects the amount of Na+ entering per impulse and the activation of the Na pump to be reduced by reducing Na+ concentration in the external medium. It is concluded that PTH in the median giant axons of crayfish is produced by at least two mechanisms. One is an increase in activity of the electrogenic Na pump, and the other is an increase of membrane conductance to K+ and Na+.