Ionic basis of tetanic and post-tetanic potentiation at a mammalian neuromuscular junction

Abstract

1. The ionic basis of tetanic and post-tetanic potentiation (TP and PTP) was studied at the rat soleus neuromuscular junction (NMJ), using the miniature endplate potential (MEPP) frequency as an index for transmitter release. Conventional intracellular recording and computer-assisted data analysis were employed. 2. The experimental results in this study indicate that contrary to previous suggestions, there is a substantial similarity in the ionic basis of TP and PTP at the mammalian and amphibian motor nerve terminals which can be subdivided into [Ca2+]o-dependent and [Ca2+]o-independent parts. 3. Tetanic and post-tetanic increase in MEPP frequency at the rat soleus NMJ is similar to that at the frog NMJ in the following aspects: (i) Tetanic potentiation is substantially larger in calcium-containing solutions than in calcium-deficient solutions. About 90% of tetanic potentiation is contributed by extracellular calcium. (ii) Increase in [Mg2+]o reduces tetanic potentiation in calcium-containing solutions and enhances TP in calcium-defient solutions. Elevated [Mg2+]o prolongs the post-tetanic potentiation both in calcium-containing and in calcium-deficient solutions. (iii) A post-tetanic jump in MEPP frequency was observed in 44% of the experiments performed in calcium-deficient solutions. (iv) The augmentation phase of post-tetanic potentiation, evident in calcium-containing solutions, is completely abolished by removal of [Ca2+]o. (v) Tetanic and post-tetanic potentiations are enhanced by increasing the rate and duration of tetanic stimulation in calcium-containing solutions. 4. The [Ca2+]o-independent part of tetanic potentiation is presumably due to entry of sodium ions and their accumulation in the nerve terminal, since it is increased by measures known to inhibit the sodium pump: reduction in [K+]o and partial substitution of sodium by lithium. 5. Sodium ions contribute substantially to the [Ca2+]o-independent part of posttetanic potentiation, since its duration is markedly prolonged by ouabain, reduction in [K+]o and partial substitution of sodium by lithium. 6. Tetanic potentiation is manifested earlier in calcium-containing media than in calcium-deficient media. This difference may indicate that sodium entry into the terminal during tetanic stimulation is at locations remote from the releasing sites. Alternatively, this time difference may be due to the delay between intracellular sodium accumulation and the increase in transmitter release.