Advances in imaging technology have allowed optical analysis of Ca(2+)-permeable ion channel activity. Here, we briefly review novel developments in optical recording of L-type voltage-dependent Ca(2+) channel (LTCC) function with high spatial and temporal resolution. Underlying principles supporting the use of total internal reflection fluorescence (TIRF) microscopy for optical measurement of channel activity and new functional characteristics of LTCCs revealed by application of this approach are discussed. Visualization of Ca(2+) influx through single LTCCs ("LTCC sparklets") has demonstrated that channel activity is regionally heterogeneous and that clustered channels are capable of operating in a cooperative, or "coupled" manner. In light of these findings, we describe a current molecular model for the local control of LTCC activity and coupled gating in physiological and pathological contexts. This article is part of a Special Issue entitled: 12th European Symposium on Calcium.
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