These figures can be put in perspective by estimating the metabolic demands necessary to maintain circulating currents on the order of 10 pA in rods with ROS volumes of approximately 0.4 pL. The demands of ATP by the Na
+, K-ATPase in the dark were estimated by assuming that (1) the inflow of Na
+ = outflow of Na
+ ∼
I Dark (circulating current), and (2) the outflow of Na
+ is mediated almost exclusively by the Na, K-ATPase. Given that 1 ATP:3 Na
+:2 K
+ is the stoichiometry of the Na, K-ATPase, then
R, the rate of ATP consumption by the ATPase is:
\[R{=}\ \frac{I_{\mathrm{dark}}}{3FV_{\mathrm{cyt}}}{=}8.6\ {\cdot}\ 10^{{-}5}\ \frac{\mathrm{moles}}{\mathrm{Lsec}}{=}5.2\ \mathrm{mM}/\mathrm{min}\]
where
I Dark = 10 pA is the circulating current in the dark,
F is Faraday’s constant, and
V cyt = 0.4 pL is the cytosolic volume of the rod outer segment. We conclude that the estimated rate of ATP hydrolysis by the ATPase (5.2 mM/min or 20 × 10
6 ATP/s) is comparable to that required to maintain constitutive GC activity (5.4 mM/min or 21 × 10
6 ATP/s). With the assumption that maintenance of the circulating currents accounts for 40% of total energy consumption,
45 the simultaneous metabolic demands of both constitutive activity and circulating currents in vitamin A–deprived rods of
Xenopus will combine to consume at least ∼80% or more of the ATP produced by normal rods. How
Xenopus rods can sustain the metabolic demands of both phototransduction and membrane potential while continuing to service other housekeeping needs is not at all clear. In mammalian rods, the allocation of energy resources allows large increments in cGMP synthesis without compromising the metabolic status of the cell. For example, in mouse rods the energy expenditure associated with the maintenance of the circulating currents is 57 × 10
6 ATP/s, whereas the ATP expenditure for cGMP synthesis (in the dark) is close to 0.1 × 10
6 ATP/s.
47 Assuming a 15-fold increase in cGMP synthesis (in analogy to
Xenopus rods), the energetic demands would rise to 1.5 × 10
6 ATP/sec. Such an increment represents <2.5% of the energy required for maintaining the circulating currents, a small amount that is unlikely to stress the rods. Hence, it appears that mammalian rods that degenerate with constitutive activity are better prepared to manage the metabolic cost of constitutive activation than are
Xenopus rods that do not degenerate under similar conditions. This notion suggests that the different capacities of these rods to recover their circulating currents probably arise from differences in the mechanisms governing the flux of cGMP. More studies are needed to decipher these mechanisms in mammalian and
Xenopus rods.