Figure 5.
Estimate of second messenger concentrations near their source, assuming free diffusion. (A) Simulation of steady state cAMP concentration near AC, k cat = 59 s−1 (see text for details). Even as close as 5 nm from AC the cAMP concentration is considerably lower than the concentration required to half-maximally activate PKA, and ∼10,000-fold lower than that required to half-maximally activate oCNG channels. (B) The high throughputs of Ca2+ channels are responsible for the high Ca2+ concentrations near the mouth of the channel. The Ca2+ throughputs (k 1 = 5 × 105 s−1, k 2 = 5 × 104 s−1, and k 3 = 5 × 103 s−1) were chosen to represent a physiologic range from the high Ca2+ throughput of voltage-gated Ca2+ channels (Hille 1992) to the low Ca2+ throughput of ICRAC channels (Zweifach and Lewis 1993). These results are similar to those of Naraghi and Neher 1997; however, Ca2+ buffering was not considered in our simulations. (C) Time course of cAMP accumulation 10 nm from AC. The steady state cAMP concentration is reached within 2 ms. These simulations demonstrate that 2-D localization of AC and oCNG channels is not enough to explain our results.