CHANGES IN CALCIUM-CHANNEL CURRENT DENSITIES IN RAT COLONIC SMOOTH-MUSCLE CELLS DURING DEVELOPMENT AND AGING

The age-related changes of Ca2+ channel currents were investigated in freshly isolated single smooth muscle cells from the circular layer of the distal colon from the rat using the whole cell voltage clamp tech nique. Under physiological conditions (Ca2+ concentration of 2.0 mM), the averaged total Ca2+ current density increased markedly from 1.25 p A/pF in the newborn rat to 6.46 pA/pF in the 60-day-old rat; it then g radually declined with aging. Two types of Ca2+ channel currents seeme d to be present; one type possessed more negative threshold potentials (-70 to -60 mV) when the cells were held at -80 or -100 mV and inacti vated quickly. The voltage for peak current was -20 to -10 mV, and the reversal potential was +60 to +70 mV. This current was highly sensiti ve to low concentrations of Ni2+ (30 muM) but was resistant to nifedip ine, diltiazem, cadmium, and tetrodotoxin. In contrast, the other type of Ca2+ channel current possessed more positive threshold potential ( -40 mV) and inactivated more slowly. The voltage for peak current was 0 mV, and the reversal potential was +60 to +70 mV. This current was i nsensitive to low concentrations of Ni2+ but highly sensitive to nifed ipine, diltiazem, and cadmium. These results suggest that the fast ina ctivating (transient) current might be T-type Ca2+ current and such ce lls were I(Ca(T)) positive cells; whereas the sustained Ca2+ current w as L-type Ca2+ current [I(Ca(L))], and such cells were I(Ca(L)) positi ve cells. Our results showed that the fraction of I(Ca(T)) positive ce lls increased with development; the current densities of both I(Ca(L)) and I(Ca(T)) also increased with development. I(Ca(T)) remained high during aging, whereas I(Ca(L)) declined. The possible physiological im plications for such changes are discussed.