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

The effects of various [Ca2+]0 on 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 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 of PK+ 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.