Acidic regulation of junction channels between glomus cells in the rat carotid body. Possible role of [Ca]i

The purpose of this work was to characterize the gap junctions between cultured glomus cells of the rat carotid body and to assess the effects of acidity and accompanying changes in Ca²⁺]_i on electric coupling. Dual voltage clamping of coupled glomus cells showed a mean macrojunctional conductance (G_j) of 1.16 nS±0.6 (S.E.), range 0.15–4.86 nS. At normal pH_o (7.43), a steady transjunctional voltage (ΔV_j=100.1±10.9 mV) showed multiple junction channel activity with a mean microconductance (g_j) of 93.98±0.6 pS, range 0.3–324.5 pS. Single-channel conductances, calculated as variance/mean g_j, gave a mean value of 16.7±0.2 pS, range 5.13–39.38 pS. Manual measurements of single-channel activity showed a mean g_j of 22.03±0.2 pS, range 1.3–160 pS. Computer analysis of the noise spectral density distribution gave a channel mean open time of 12.7±1.5 ms, range 6.37–23.42 ms. The number of junction channels, estimated in each experiment from G_j/single-channel g_j, showed a range of 7 to 258 channels (mean, 107.2). Optical measurements of Ca²⁺]_i gave a mean value of 80.2±4.27 nM at pH_o of 7.43. Acidification of the medium with lactic acid (1 mM, pH 6.3) induced: 1) Variable changes in G_j (decreases and increases); 2) A significant decrease in mean g_j (to 80.36±0.34 pS) and in single-channel conductance (g_j=12.8±0.2 pS in computer analyses and 17.23±0.2 pS when measured by hand); 3) Variable changes in open times, resulting in a similar mean (12.8±1.5 ms) and 4) No change in the number of junction channels. When pH_o was lowered to 6.3 Ca²⁺]_i did not change significantly (there were increases and decreases). However, when pH_o was lowered to 4.4, Ca²⁺]_i increased significantly to 157.1±8.1 nM. It is concluded that saline acidification to pH 6.3 depresses the conductance of junction channels and this effect may be either a direct effect on channel proteins or synergistically enhanced by increases in Ca²⁺]_i. However, there are no studies correlating changes of Ca²⁺]_i and intercellular coupling in glomus cells. Stronger acidification (pH_o 4.4), producing much larger changes in Ca²⁺]_i, may enhance this synergism. But, again, there are no studies correlating these effects.