Dual effects of calcium ions on pacemaker activity in guinea-pig taenia coli

The effects of various [Ca²⁺]₀ tn membrane potential (MP), action potential (AP) frequency, and isometric tension of isolated guinea-pig taenia coli were studied using intracellular recording techniques and simultaneous tension measurement. At 5.9 mM [K⁺]₀ the order of potency of [Ca²⁺]₀ to increase AP frequency is 0.83>2.5>7.5 mM. At higher [K⁺]₀ this order is gradually reversed since high [Ca²⁺]₀ becomes more potent in accelerating impulse discharges. At 2.5 mM [Ca²⁺]₀ the line relating MP to log [K⁺]₀ is not straight; its slope for a tenfold change of [K⁺]₀ is 21.1 mV in the range between 5.9 and 17.7 mM [K⁺]₀, and 51.5 mV between 32.45 and 59 mM [K⁺]₀. In general, reducing [Ca²⁺]₀ depolarizes the membrane whereas increasing [Ca²⁺]₀ hyperpolarizes it. The Ca²⁺-induced changes of MP are reduced at high [K⁺]₀. At 2.5 and 7.5 mM [Ca²⁺]₀ the lines relating AP frequency and tension to the MP are nearly superimposed. In contrast, at 0.83 mM [Ca²⁺]₀ the line is shifted to lower frequency and tension for all MP values studied. In conclusion, in the range of low [Ca²⁺]₀ the system underlying pacemaker activity seems to be dependent on Ca²⁺ in two ways: 1. by an indirect negative action mediated by an increase ofP\(P_{{\text{K}}^{\text{ + }} } \) and by hyperpolarization of the membrane; 2. by a direct positive action which is not mediated by alterations of MP. In the range of normal and high [Ca²⁺]₀ only potential-mediated Ca²⁺-effects determine AP frequency. The hypothesis is put forward that Ca²⁺ may carry the background inward current responsible for pacemaker activity.