Effects of strontium on the permeation and gating phenotype of calcium channels in hair cells.
To minimize the effects of Ca2+ buffering and signaling, this study sought to examine single Ca2+ channel properties using Sr2+ ions, which substitute well for Ca2+ but bind weakly to intracellular Ca2+ buffers. Two single-channel fluctuations were distinguished by their sensitivity to dihydropyridine agonist (L-type) and insensitivity toward dihydropyridine antagonist (non-L-type). The L- and non-L-type single channels were observed with single-channel conductances of 16 and 19 pS at 70 mM Sr2+ and 11 and 13 pS at 5 mM Sr2+, respectively. We obtained KD estimates of 5.2 and 1.9 mM for Sr2+ for L- and non-L-type channels, respectively. At Ca2+ concentration of approximately 2 mM, the single-channel conductances of Sr2+ for the L-type channel was approximately 1.5 and 4.0 pS for the non-L-type channels. Thus the limits of single-channel microdomain at the membrane potential of a hair cell (e.g., -65 mV) for Sr2+ ranges from 800 to 2,000 ion/ms, assuming an ECa of 100 mV. The channels are >or=4-fold more sensitive at the physiological concentration ranges than at concentrations>10 mM. Additionally, the channels have the propensity to dwell in the closed state at high concentrations of Sr2+, which is reflected in the time constant of the first latency distributions. It is concluded that the concentration of the permeant ion modulates the gating of hair cell Ca2+ channels. Finally, the closed state/s that is/are altered by high concentrations of Sr2+ may represent divalent ion-dependent inactivation of the L-type channel.
Rodriguez-Contreras
Adrian
A
Center for Neuroscience, Program in Communication Science, University of California, Davis, 1544 Newton Ct., Davis, CA 95618, USA.
Lv
Ping
P
Zhu
Jun
J
Kim
Hyo Jeong
HJ
Yamoah
Ebenezer N
EN
D000818:Animals; D001464:Barium / Q000378:metabolism / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism; D020013:Calcium Signaling; D003627:Data Interpretation, Statistical; D006198:Hair Cells, Auditory / Q000187:drug effects*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects*; D008564:Membrane Potentials / Q000187:drug effects; D018408:Patch-Clamp Techniques; D010539:Permeability; D011892:Rana catesbeiana; D013324:Strontium / Q000378:metabolism / Q000494:pharmacology*
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D001464:Barium; D013324:Strontium