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.