(27) CA2+ SIGNALING TO MITOCHONDRIA VIA RaM: HOW IT MAY DIFFER FROM SIGNALING VIA UNIPORTER

T. Gunter, L. Buntinas and K. Gunter
Department of Biochemistry and Biophysics, University of Rochester, Rochester, NY

There are two primary differences in the Ca2+ sequestered into mitochondria via the rapid mode of uptake (RaM) and that sequestered via the uniporter from the point of view of intracellular signaling: 1) The RaM conveys aspects of frequency modulated signaling on the system, and 2) The intramitochondrial [Ca2+]m may be significantly larger following Ca2+ uptake via RaM than following uptake via uniporter. In liver mitochondria RaM mediates Ca2+ uptake at the beginning of each pulse of a sequence of pulses and uptake via RaM can represent a large fraction of total Ca2+ uptake. This makes the final value of total Ca2+ within the mitochondria at the end of the pulse sequence more dependent on the number of pulses in the sequence and on the frequency of the pulses than on the amplitude of the pulses.

The rate of Ca2+ uptake via RaM is at least a factor of 30 times faster than that of the uniporter under the same conditions and probably of the order of a hundred or more times faster. The bulk of intramitochondrial Ca2+ and Mn2+ have been shown to bind to sites on the inside of the inner membrane and to displace protons from their binding sites in this process. Since 1 or 2 H+ must be displaced before a Ca2+ can bind, this binding is a slow process. This means that it is likely that [Ca2+]m can become significantly higher following Ca2+ uptake via RaM than following Ca2+ uptake via the uniporter. If Ca2+ binding to activation sites within the metabolic pathways is sufficiently rapid, then Ca2+ uptake via RaM could activate these pathways at a much lower total Ca2+ uptake than could Ca2+ uptake via the uniporter.

Supported by AHA NY State Affiliate Grant # 960166.